LMLechko
Monday, June 28, 2004
alkenes
1. Important definitions:
saturated: Containing only single bonds between carbon atoms unable to accommodate additional hydrogens.
unsaturated: Containing one or more double (=) bond or triple () bonds and able to accommodate additional hydrogens.
alkenes: Containing only carbon and hydrogen and a least one double bond.
alkynes: Containing only carbon and hydrogen and at least one triple bond.
Nomenclature
1. Naming the alkenes and the alkynes.
2. Find the root of the name as you would in the alkane. The longest unbroken chain.
3. You than must determine if there is a double or a triple bond present in the compd.
If there is a double (=) bond, the suffix of ene replaces ane.
i.e. pentane -----> pentene
hexane -----> hexene
If there is a triple () bond, the suffix of yne replaces ane.
In order to properly identify this compd., start with the longest chain containing the double or triple bond. Begin the count nearest the double or the triple and affix the proper suffix.
The same is true of the triple bonds ().
The condensed formulas for the next three structures are shown below. Note in each case the double and triple bonds are shown.
4. Step 3: Indicate by numbers the positions or the alkyl groups attached to the parent chain.
Name ---> 7-methyl-2-octyne
not 2-methyl, 6-octyne
again, 7-methyl ---> prefix
2 ---> prefix
oct ---> root
yne ---> suffix
5. Even if both a halogen and an alkyl group are found in the same compd, still start at a position as close as possible to the double or triple bond. When possible assign the lowest possible total assignments. Cite in alpha order.
6. If there are multiple halogen attached, than the appropriate designations of di, tri, tetra, etc must be affixed.
7. Here is what happens if you have multiple alky groups in the same compd. Start nearest the first branch in this example.
Geometric Isomerism
1. In describing the geometry of organic compds, if there are four separate bonds attached to a central carbon atom, than the geometry about that carbon is described as tetrahedral.
2. In describing the geometry of organic compds, if there are two single bonds and one double bond attached to a central carbon atom, then the geometry about that carbon is described as planar.
3. In describing the geometry of organic compds, if there are two double bonds attached to a central carbon atom, than the geometry about that carbon is described as linear. O=C=O
4. In describing the geometry of organic compds, if there is a single and a triple bond attached to a central carbon atom, than the geometry about that carbon is described as linear. H-CC-H
5. When there are carbon - carbon single bonds, there is always free rotation about that bond, giving rise to an infinite number of conformations, which are NOT isomers.
6. The presence of the double bond introduces a new form of isomerism, geometric isomerism. In particular, it is described as cis-trans isomerism. It is geometric because the arrangement of the groups about the double bond is changed.
7. Cis and trans isomerism also occurs about the double bond in a linear alkenes and cycloalkanes.
8. Cis/trans isomerism need not be limited to hydrogen. Anytime two halogens or groups are either on the same side or opposite each other, geometric isomerism exists.
8. Isomerism comes in many forms, it is the word used to described circumstances. Geometric isomerism is a special case of isomerism.
Cis Isomer: Isomer having a specific pair of atoms or groups on the same side of the double bond. The word cis is appropriately described as a prefix.
Note: The designation CH3 = H3C, JUST WRITTEN DIFFERENT.
A incorrect name for the compd. would be cis 1, 2-dimethyl ethene. The reason is that you must count each of the carbons in the longest continous chain. There are four carbons present with a double bond found on the second carbon. The appropriate name would be: a 2-butene.
Each of the above representations are the same. The double bond is found on C#2. One is written to be read easily, the other is not.
Representations
1-butene, 2-butene, and 2-methyl propene are isomers of each other, only 2-butene has cis/trans.
Cis/trans 2-butene is sufficient to identify the compd. You need not worry about identifying the locations of the hydrogens. It is understood that they are there: the absence of a prefix for the presence of other groups.
However, if the compd. was as follows:
As written is confusing, however, within the limitations of the paper, both groups pointing in the same direction (up/down) indicates cis/trans isomerism.
Trans Isomer: Isomer with a specific pair of atoms or groups on the opposite side of the double
bond.
9. One caveat: THERE CAN BE NO CIS TRANS ISOMERISM IF TWO IDENTICAL GROUPS ARE ATTACHED TO ONE OF THE CARBONS INVOLVED IN THE DOUBLE BOND. (Some C - H bonds omitted for simplicity.)
Here two fluorine atoms are attached to C#1, therefore no cis/trans isomerism.
Given ethene with two fluorine atoms attached, there are three possible isomers.
A, B and C are geometric isomers of each other.
cis 1,2 trans 1,2 1,1-diflouroethene
There can be no cis/trans isomerism in a triple bond because the molecule is linear!
Possible arrangement of cis/trans depends on the relationship of four groups to each other!
Properties of Alkenes
1. To be an alkene, you must have a double (=) bond between two carbon atoms.
2. If a carbon compound has three or more carbons, the compd. may have both alkane and alkene like character.
3. Alkenes are non polar, with b.p. and m.p. increasing with increasing carbon length. B.p. and m.p. lower than corresponding alkane.
n-butane vs. 1-butene
b.p. ºC O -6.5
4. Solubility decreases with increasing carbon length.
5. Cis and trans isomerism is possible about double bond.
6. The double bond undergoes addition and oxidation Rxs.
Nomenclature of the Alkynes
1. Named systematically as in the alkanes.
2. Simplest alkyne is:
H-CC-H ethyne
Name root ---> ethane
drop ane and add yne ---> ethyne
H-CC-CH3 ---> propyne
propane ---> propyne
not 1 propyne because no substitutions
Again, always assign the lowest possible number to the triple () bond.
3. Complex names for alkynes have the prefix, root and suffix. This condensed formula clearly shows this relationship.
In this case, the triple bond ended up in the same place as in the previous example, however, the branch has a higher number assigned. Need the lowest possible number for the branch. Hence, the functional group is first followed by the branch point.
Properties of Alkynes
1. Non polar compds.
2. Undergo addition and oxidation reactions.
3. M.p. and b.p. similar pattern to corresponding alkane.
4. Solubility decreases with increasing carbon number.
5. Geometry is linear across triple bond.
6. No cis/trans isomerism across triple bond: not possible because triple bond geometry is linear.
Reactions of Alkenes and Alkynes
1. Alkenes and alkynes will typically undergo addition Rxs. Addition Rxs occur across the double bond, which is the functional group and the substitution Rxs will occur across the single bonds, which are the alkane functional group. Where addition or a substitution reaction occurs depends on the reaction conditions employed.
Addition Reaction: Addition of a reactant of the general form X-Y to the multiple bond of a unsaturated compd. to a yield a saturated product, containing only single bonds. Two forms:
a. X2: (H2, Cl2, I2)
b. HX: (HCl, HI HBr, HOH)
A. Catalytic hydrogenation: unsaturated ---> saturated
Hydrogenation: Rx of an alkene or aklyne with hydrogen in the presence of a metal catalyst [M] to yield an alkane product.
General form:
* Always assign the lowest number to branch point in an alkane. Note the change in the ending from ene to ane.
In the above alkenes, the hydrogens could be cis or trans prior to hydrogenation, however, once fully hydrogenated, cis/trans relationship ceases to exist. This is true because there is free rotation about the carbon – carbon single bonds.
Process can also occur in a(n) cyclic alkene.
+ H2/M
cyclohexene cyclohexane
no cis/trans no cis/trans
In the previous examples, hydrogens are not shown, need not show them. The condensed structures of the rings are sufficient. If something other than hydrogen was added, than you need only to show the group(s) which were added.
+H2/M
1-methylcyclohexene ---------> methylcyclohexane
Need to identify the location of the methyl group prior to hydrogenation. If said only methylcyclohexene, these would be another possible structures:
all are isomers
(hydrogen omitted)
3-methyl 4-methylcyclohexene
Prior note the change from ene to ane. As always, there could be cis/trans isomerism across the double bond.
B. Halogenation: Addition of the following halogens
a. Cl2
b. Br2
c. I2
Halogenation alkene: Addition Rx of a halogen to yield a dihaloalkane.
Halogenation alkyne: Addition Rx of a halogen to yield a tetrahaloalkane.
General form: (mixing reactant and halogen)
Process can also occur in the cycloalkene
+ Br2/CH2Cl2 ----->
(CH2Cl2 is a solvent)
cyclohexene 1, 2-dibromocyclohexane
+ Br2/CH2Cl2 ----->
1-methylcyclohexene 1, 2-dibromo, 1-methylcyclohexane
Knowledge Challenge:
+ Cl2/light ----->
1-methylcyclohexene 1-chloromethylcyclohexene
3-chloro-1-methylcyclohexene
C=C takes highest priority
Note: written in alpha order
C. Hydrohalogenation: The Rx to a alkene with HCl of HBr to yield an alkyl halide.
X = halogen a. HCl
b. HBr
Where the hydrogen and the halogen finally end up is determined by the following rule of addition:
Markovnikov'sRule: In the addition of HX to an alkene the hydrogen becomes attached to the carbon that already has the most hydrogens (primary carbon) and the halogen becomes attached to the carbon with the fewest, secondary or teritary).
Process include:
1. hydrohalogenation
2. hydration
Remember: halogenation =/= hydrohalogenation
Halogenation is the addition of the diatomic halogen across the double or the triple bond.
Hydrohalogenation involves the addition of HX across the double bond. Where X = chlorine, bromine or iodine.
General form:
For those who wanted to know --> the addition of non identical adgenda (HX) to a triple bond follows Markovnikov's Rule. (All you would ever want to know).
In order for this process to be succeed, the concentration of the alkyne and haloalkene must be in significant excess!
Addition to Cycloalkenes
Markovnikov's Rule: The addition of HX to an cycloalkenes included the hydrogen becomes attached to the carbon that already has the most hydrogens and the halogen becomes attached to the carbon with the fewest.
HOH
(ACID)
1-methylcyclohexene 1-methyl-1-cyclohexanol
tertiary carbon tertiary alcohol
+ HCl ---->
cyclohexene chlorocyclohexane
+ HBr ---->
1-methy-1cyclohexene 1-bromo-1-methylcyclolohexane
1. Oxidation: Process in organic chemistry is described as the loss of electrons or hydrogens or the gain of oxygen.
It's collerary --> reduction: The loss of oxygen or the gain of electrons or hydrogen atoms.
Alkenes┆__________ + O2 + heat ----> CO2 + H2O (combustion)
Alkynes┆
D. Hydration alkene: The Rx of an alkene with water and acid to yield an alcohol. Water adds to the more reactive alkenes. Addition follows Markovnikov's Rule.
General form:
Hydrogen attaches to C#1 a 1 (primary carbon) -OH attaches to C#2 ==> teritary alcohol
Hydration can also occur in the cycloalkenes. What you need to know about the hydration of the cycloalkenes is limited to the understanding that all cycloalkenes can undergo addition as determined by:
Polymers
1. Polymers are large molecules formed by bonding together many smaller molecules called monomers.
2. These monomers may be identical or different.
3. The molecular weight of the polymers tend to be very large.
4. Many of the common materials you encounter are polymers.
5. Many biological materials are polymers.
6. Polymers do not have to be made up only of alkenes.
7. One of the most common polymers that you encounter every day is PVC, polyvinyl chloride.
8. PVC is made up of the repeating unit called the vinyl group, H2C=CH , or in IUPAC name of ethenyl.
9. Ethylene, H2C=CH2 which is the starting material is polymerized. Polymerization is the process of linking monomers together to form a polymer.
10. The process is described as being chain growth. Meaning that you add one monomer at a time.
11. Like many processes that we have discussed, the process requires a catalyst, however in polymer terms it is called a initiator.
12. Using careful techniques, the molecular weight of the polymer can be controlled. This is important when you want certain properties or the ability to process the polymer. You can also control branching as well.
13. The longer straight chains w/o branching allows for close packing of the chains, giving rise to a rigid structure, having a higher m.p. ==> rigid or high density ==> plastic bottles. Remember increasing the number of (-CH2-) increasing b.p. and m.p. of linear alkanes. Those with branching ==> low density, and more flexible applications ==> plastic wrap.
Aromatic Compds
1. Aromatic compds: A description of a class of compds containing benzene-like rings. Can be heterocyclic as well.
benzene a heterocylic
2. The molecule is described as being held together by resonance. This is the type of molecule in which there is no proper way to describe the carbon to carbon bonding relationships. It is frequently described as an electron smear. The bonds that form are not double but not single. They are somewhere between. The structures below represent the possible triene relationship that could describe the possible relationship, however, singlely, neither is correct. Hence the name, electron smear!
electron smear
3. A benzene ring that is unsubstituted, is non polar, insoluble in water and not very reactive. Aromatic compds will not react with H+ (hydrogenation), HBr and HCl (hydrohalogenation) and H2O (hydration) under conditions which will reaction with other alkene or alkynes.
4. Benzene like rings are frequently found in many biomolecules. Including the DNA and RNA.
Indole Adenine
(perfume) (DNA/RNA)
Nomenclature Aromatic Compds
1. Start with the parent compd. in most cases: Benzene
2. Then name as a substituted derivative of benzene.
Bromobenzene Ethylbenzene Nitrobenzene
There is only one group on the ring, therefore it is assumed to be C#1. Named as 1 bormobenzene is WRONG!
3. Disubstituted aromatic compds are name using one of the following prefixes, instead of C#1, 2 or 3. Positions described relative to each other in the benzene ring. The use of these prefixes occurs instead of the naming by locants.
a. ortho ===> 1, 2
b. meta ===> 1, 3
c. pare ===> 1, 4
ortho meta para
4. If groups are identical, in the disubstituted ring apply the prefix di.
o-dichlorobenzene m-dichlorobenzene p-dichlorobenzene
5. If the groups substituted are different, you number in alpha order. For testing purposes, disubstituted is where we stop.
p bromochlorobenzene m chloroethylbenzene
6. Many substituted aromatic compds have common name in addition to IUPAC names. It is a good idea to memorize the name and structure. You will encounter them in lab, exercises and elsewhere.
phenol Nitrobenzene Toulene
Aniline Benzoic Acid Benzaldehyde
7. If the previous compds have an additional group attached, than the designations of ortho, meta and para is used in conjunction with the common names above.
p-chlorotoulene m-chlorotoluene o-chlorotoulene
m-nitrophenol o-chlorophenol p-bromophenol
8. Sometimes the benzene ring is considered to be a substitutent, when this happens, the name phenyl is applied.
3-phenlyheptane
Reactions of Aromatic Compds
1. Aromatic compds undergo several types of reactions. These reactions are described as substitution reactions. These reactions are of the form YX.
XY ----> + H-Y
benzene
a. Nitration: Substitution of an NO2 for an -H in an aromatic ring
HNO3/H2SO4 ----> + H2O
benzene nitrobenzene
Useful for the production of aniline which is used in many clothing dyes and explosives. TNT is made in a stepwise process: The structure looks something like this: No I can not tell you have the process is exactly done!
Toluene TNT
trinitrotoluene
2, 4, 6-trinitrotoluene
HNO3/H2SO4---->
Aniline p-nitroaniline
Aniline name used because you started with aniline, just simpler. Could be named p amino nitro benzene.
b. Halogenation: Substitution of -Br or -Cl for -H in an aromatic ring.
Cl2/Fe ---->
benzene (Fe = catalyst) chlorobenzene
Cl2/Fe ---->
chlorobenzene p dichlorobenzene
Cl2/Fe ---->
aniline o-chloroaniline
c. Sulfonation: Substitution of SO3H for an H in an aromatic ring.
H2SO4/SO3 ---->
benzene benzenesulfonic acid
Useful for the production of sulfa-related drugs.
Cl2/Fe -->
benzenesulfonic acid o-chlorobenzenesulfonic acid
d. Hydration: Addition of water, making an alcohol. For exam purpose, recognize that this is the addition on a -OH group to a aromatic or a polyaromatic compd. Know how to get there for a single aromatic compd. only! This hydration process is the "culprit" in the creation of some carcinogens in some polyaromatic compds.
benzene phenol
Cl2/Fe ---->
phenol p-chlorophenol
Hydrogenation: Addition of hydrogenation. Taking a aromatic compd. and making it a fully saturated hydrocarbon. This is an addition reaction.
H2/metal ---->
benzene cyclohexane
Polyaromatic Compds
1. A(n) organic compd. that has two or more "benzene" like rings fused along their edges is called a polyaromatic compd.
Napthalene Benz[a]pyrene
Both of these compds fall into this classification. What makes them "benzene" like is the
presence of resonance. Each of the rings is capable of undergoing the typical aromatic substitution reactions.
Napthalene: Found in mothballs. It has a high m.p. It will change from a solid to a gas slowly. A process of ?
Benz[a]pyrene: Carcinogenetic. Found in soot. Found in cigarette smoke and burnt meat. Exposure to small quantities can cause tumors.
The problem with Benz[a]pyrene is when the body attempts to rid itself of the compd. by converting it to a alcohol, a process of oxidation, a hydration reaction. Unfortunately, the new compd. binds to cellular DNA and causes a mutation. This is case where the body creates a carcinogen by "trying" to get rid of a foreign compd.
Typically detoxification reactions occurs in the liver. The changed metabolite then moves throughout the body carried blood plasma. Many cancers of this sort tend to be liver cancers, since the concentration of the carcinogen tends to be concentrated in one organ. This is true of many carcinogens if a chemical has an affinity for a "target".
Dyes and Color
Many of the polyaromatic rings are found in dyes.
One of the most important of the fused rings compds is beta carotene, an analogue of Vitamin A which is we know is needed for vision. Have you ever seen a blind rabbit?
Remember, the color that we see, is complementary to the color absorbed. That is, we see what is left of the white light after certain colors are absorbed. Different dyes have different chemical structures. It is these structures which determine the color which is absorbed, that is the color of the dye that we see!
When we treat a compd. with bleach, we are breaking up the resonance in the compd. Therefore, that is why a green compd. treated with bleach becomes white. It is not
Monday, June 21, 2004
Proteins
• protein: a large biomolecule, really a polymer of many amino acids linked together by amide(peptide) bonds
• amino acid: a molecule that contains both an amino group and a carboxylic acid functional group
• amino acid: an amino acid in which the amino group is bonded next to the –COOH group
• peptide bond: an amide bond that links two amino acids together
• each amino acid contains an “R” group and an amino group bonded to a central carbon atom
• amide bonds are called peptide bonds when they occur in proteins
• a dipeptide results from bonds two amino acids together; one from the amino group and one from the carboxylic acid group of the neighboring amino acid
• tripeptide is three amino acids
• linear chain like polymer of amino acids is a polypeptide
• the exact order of sequence of this unfolded, linear chain is called primary sequence; which is determined by the information strand of DNA. This is responsible for the following protein structures:
o secondary: repeating spatial organization
o tertiary: overall shape produced by bending and folding
• quaternary: relationship of two or more polypeptide chains in their 3-D configuration
• see table 18.2 page 486 for classification scheme based on function
• structure: collage and keratin; fingernails and hair
• catalysts: enzymes
• contractile proteins: mechanical work, actin and myosin
• protective: IgG, IgA, IgM
• storage: myoglobin holds oxygen in muscle tissue
• transport: albumin which carry endogenous lipid in the circulatory system
• hormones: polypeptide and polypeptide derivatives
Amino Acids
• nature uses 20 common amino acids in the building proteins
• see table 18.1 page 484: important function groups
a) need to know each functional group
• see table 18.3 page 487:
a) know classifications
b) do not need to know where each one fits
• 19 have chiral centers, glycine does not
• 19 of the amino acids are similar in that they a primary amines and only proline is a secondary amino acid
• also glycine is the simplest of the amino acids which have as an “R” group hydrogen
• typically describe name of the amino acid w/ a 3 letter code
• the twenty amino acids are classified in the following manner and would have the following characteristics:
a) non-polar side chains
1) hydrophobic in character
2) tends to be found in the center of a folded protein and
3) participates in London Force
4) creates a water free environment
b) polar and neutral side chains
1) forms hydrogen bonds
2) hydrophilic
c) acidic
1) hydrophilic
2) ionic
3) salt bridge w/ base
d) basic
1) hydrophilic
2) ionic
3) salt bridge w/ acid
central theme points:
1) covalent bonds
a) disulfide bonds
2) ionic
a) salt bridges
3) others
a) hydrogen bonding
b) London forces
c) hydrophobic between the non polar
R groups pf the protein
KEY= water loving AAs tend to be found on the surface of the protein this gives solubility to the protein in water
Acid Base Properties of Amino Acids
• zwitterions: a neutral dipolar ion that has one + and one – charge
• this results when a –COOH group gives up a proton and a –NH2 takes on a proton at physiological pH
• the result:
• is a COO-
• and a NH3+
• a dipolar ion
• AAs should be written in their ionized forms
• because they are ions, they have the following properties
o crystalline
o high melting points
o soluble in water but not hydrocarbon solvents
o behave as acids or bases (all acid/base groups) behave differently
o in acid solution, they accept hydrogen ions on the basic COO-
• see page 490
o in basic solutions lose proton from their acid –NH3+
• see page 490
o the structure and charge of an amino acid depends on the pH environment
• isoelectric pH: IpH; the pH region in which the in a given sample of an amino acid or a protein, there is an net equal number of positive and negative charges
o any point below the Ip there is a net + charge
an acid soln.
o any point above the Ip there is a net – charge
a basic soln.
o repulsive forces smallest at the Ip
then the proteins tend to clump together and become insoluble as the groups interact and become bonded together
proteins are least soluble at their Ip
• can be used as an effective tool for separating protein chains with identical or similar MW but different amino acid composition
Handedness
• chiral: having right or left handness, able to have two different mirror images
• achiral: the opposite of chiral; having no right or left handness and no non-superimposable mirror image
• not all things have handedness
• if have handedness have lack of symmetry
-O - C = O O = C – O-
| |
+H3N-C-H H - C – NH3+
| |
CH3 CH3
L-alanine R-alanine
L the amino groups points to the left
propane has a symmetry plane
What determines if a molecule is chiral?
1) can predict from structure of molecule
2) chiral compound have four different groups bond to central carbon. Can have more than one chiral
center in a compound
• the two mirror images of a chiral molecule like alanine are called enantiomers or optical isomers because of their effect on polarized light
• stereoisomers: isomers that have the same molecular formula but different spatial arrangements of their atoms
• shared properties of alanine enantiomers:
mp
density
solubility
Ip
density
• differing properties of alanine enantiomers:
opposite directions on polarized light
react w/ other molecules
odor
taste
toxicity
drug activity
Primary Protein structure
• primary protein structure: is the sequence of a protein in which the amino acids are lined up end to end and in order, connected by peptide bonds
o the “R” groups are just substituents and do not contribute to the primary structure
o determines the secondary and tertiary structure of the protein
that is the manner in which it twists, turns, and folds on itself to produce its final 3-D shape
• sequence is what allows the protein to carry out its job
o one specific order can do the job
o one AA change can affect how a protein behaves as in the case of sickle cell hemoglobin:
Ingram and Pauling 1954
single amino acid substitution in the chain
valine is present in place of glutamine on position 6 of the chain of a polypeptide chain 574 amino acid in length
this substitution replaces a polar amino acid with a non polar amino acid
• which results in reduced the solubility of oxygenated hemoglobin
• this causes a “sticky” effect and causes a sickling effect when there is inadequate of oxygen
• occurs in the blood capillaries
• sickling can block the capillaries
• these cells are destroyed by the body defenses resulting in anemia
o in the case of human insulin which has two amino acid chains for a total of 51 AAs, the chains are connected by a disulfide bridge
sequence determined by Sanger 1958
o if you are an insulin dependent diabetic you might take insulin from the following sources below
o they are similar, but not as active as human insulin
o can be become allergic, due to an antigenic response to a foreign protein
o the chart below displays the four locations in which the substitute insulin differs from human insulin
A chain B chain
human -Thr-Ser-Ile- -Thr-
Bovine -Ala-Ser-Val- -Ala-
Hog -Thr-Ser-Ile- -Ala-
Sheep -Ala-Gly-Val- -Ala
General information:
• note there is one N-terminal end
• note there is one C-terminal end
• N-terminal comes from the 5’ end of informational strand
• C-terminus comes from the 3’ end of that same informational strand
• this is a rigid planar unit between adjacent amino acids
• by convention the N-terminal is on the left
• by convention the C-terminal is on the right
• residue: any amino acid unit in a polypeptide
• a polypeptide is named by citing the amino acid residues in order starting at the N-terminal end using “yl” endings and the C-terminal end, ends in “ine”
• no matter how long the chain becomes, there is always only one N and one C terminal end
Note: some diabetics have not be successful with insulin
produced by recombinant DNA techniques. They
express the problem as not having enough of what
is called hypoglycemic awareness
Shape Determination Interactions
• w/o interactions between atoms in amino acid side chains or along the backbone, protein chains would also be in a random coil arrangement
• the essential structure-function relationship is predicated on the 3-D structure of the protein or enzyme
• Types of interactions:
o hydrogen bonds along the backbone: hydrogen bonds form when a hydrogen atom is attracted to another highly electronegative atoms that has an unshared pair of electrons:
see figure 18.4
-NH- with –C=O
between neighboring backbone segments
results in helixes and pleated sheets
creates rigid structure
often involves adjacent atoms
• Hydrogen Bonds of R groups with Each Other or with Backbone Atoms
o see figure 18.4
o stabilize a loop
o whenever AA side chains contain atoms which can form hydrogen bonds, such bonds can be connect nearby and distant amino acids:
-NH- with –C=O
-OH with –NH-
-OH with –C=O
• phenol group with a carbonyl group
• Ionic_Attractions between R groups (salt bridges):
o see Figure 18.4
o when there are ionized acidic and basic groups
o attraction of + and – charges
can stabilize a loop
• a basic lysine with an acidic asparate
• amine group with a carboxylic acid group
• Hydrophobic Interactions Between R Groups
o see figure 18.4
o weaker than hydrogen bonds
o acts over larger surface area
net effect is to stabilized a loop
o non-polar hydrophobic chains cluster together in the same way oil drops cluster together
o typically found in center of a globular protein which is water free
creates a water free pocket
• alanine and leucine
• benzene ring with an isopropyl group
• Covalent Sulfur-Sulfur Bonds; called a sulfur bridge
o see page 500
o can stabilize a loop by oxidizing Rx
o can occur between two separate chains as in insulin
o under conditions of oxidation, two cysteine AA can react together to form a disulfide bond creating a loop
• insulin
o if two cysteines are in different chains, the chains can be linked together by disulfide bonds
insulin also provides a good example
Secondary Structure of Proteins
• secondary structure: regular and repeating structural pattern created by hydrogen bonding between backbone atoms in neighboring segments of protein chains, so that certain patterns repeat themselves
o this is the steric relationship of the amino acid residues which are close to each other in the linear sequence, some are of a regular kind giving rise to a composition of periodic structure
• alpha helix: secondary protein structure in which a protein chain forms a right handed coil stabilized by hydrogen bonds between peptide groups along its backbone
o Pauling and Correy
o similar to a tightly coiled telephone wire cord
o similar to that of a spring
shape maintained by numerous intramolecular hydrogen bonds that exist along its backbone
found in DNA
o stabilized by –C= O (carbonyl) and –NH- (amide hydrogens four resides down along chain)
• pleated sheet: secondary protein structure in which adjacent protein chains in the same or different molecules are held together in place by hydrogen bonds along the backbone
o be definition not quaternary
o Pauling and Correy
o orderly arrangement maintained by intermolecular hydrogen bonds to adjacent chains
o sheet tends to be fully extend, not tight coil as in alpha helix
regular pattern of hydrogen bonds
chains run can side by side to each other
chain arranged in anti-parallel arrangement chain # 1 N-terminal ------ C-terminal
chain # 2 C-terminal ------ N-terminal
o silk
chains can also run parallel
o within the same chain could form a U shaped segment; intra-chain, this is called the β turn which creates a hair pin loop and then the pattern repeats of the rungs on the ladder repeats
See Figure 18.6 page 503
Protein chains lie side by side to each other
alternating chains create anti parallel arrangement
can stack as sheets
inter-chain arrangement
random coils: protein configurations that do not exhibit a repeated pattern
Secondary Structure in Fibrous and Globular Proteins
• protein can also be classified in other ways:
fibrous
globular
• fibrous proteins: a tough, insoluble protein whose protein chains form fibers or sheets
o determined primarily by secondary structure
o mostly keratin
pairs of helixes are twisted together into small fibrils, which are then used as a subunit to build larger bundles
o fibroin is mostly pleated sheet
• another pattern which is classified as secondary structure is the triple helix of collagen
o third example of a periodic structure arrangement
o special arrangement of the primary structure which allows for three polypeptide chains to come together
o each strand is made of repetitive units that can be symbolize as Gly-X-Y
o every third amino acid is glycine
o glycine has a short “R” group which allows for close packing
o X is frequently proline
o Y is often hydroxyproline
o triple helix units together constitute what is called tropocollagen
an association of triple helixes results in quaternary level or organization
collagen is made up of many units of tropocollagen
connective tissue of:
• bone
• cartilage
• tendons
• aorta
• skin
• globular proteins: a water soluble protein who chain is folded in a compact shape with hydrophilic groups on the outside
o tertiary, include levels of secondary structure
o when protein chains fold back on themselves:
o can result form helixes and pleated sheets
o see protein classification chart 18.4 page 504
Tertiary Protein Structure
• tertiary protein structure: the way in which an entire protein chain is coiled and folded into a specific 3-D shape.
depends primarily on interactions of amino acid side chains that are far apart along the same backbone
determined by primary sequence
maximum stability
creates a native protein: a protein with the shape in which is exists naturally
non-covalent and disulfide bonds can also govern tertiary structure
• proteins can also be classified in another way:
simple: contains only AAs following hydrolysis
conjugated: upon hydrolysis;
• AAs
• plus a non-protein non amino component
o the two together allows the protein to be active
• see table classification 18.5 page 506
Quaternary Structure
• Quaternary Structure: the way in which two or more proteins chains aggregate to form a large order structure non-covalent interactions
• Hemoglobin:
o globular protein
o quaternary structure
o four subunits
o held together by hydrophobic attractions
o each pair contains one heme unit
• collagen:
o fibrous protein
o found in bone
o found in dentine of teeth
o found in tendons
o basic unit is tropocollagen which is then intertwined with other tropocollagen units resulting
crosslinking pattern which called quarter staggered arrangement
• units (tropocollagen) are not aligned end to end, but are staggered
• units are separated by a gap which are a nucleation for the growth of calcium crystals in bone
o facts about tropocollagen
three chains wrapped around each other
each chain is about 1000 AAs in length
these chains are then cross linked and overlapped together:
• calcium hydroxyapatite fills in gaps of the cross linked structures
Chemical Properties of Proteins
• protein hydrolysis:
o reverse of protein formation
o peptide bonds are broken
o result is a pool of amino acids
o breaking down of primary structure
HCl
• digestion of proteins in stomach and small intestine
• denaturation: the loss of secondary, tertiary, and quaternary protein structure due to the disruption of non-covalent interactions and/or disulfide bonds that leaves the peptide bonds intact of the primary structure
• the 3-D structure is really a delicate balance of non-covalent interactions
• change balance will change 3-D shape
• when 3-D shape disrupted, a random coil results
• when denatured, the net effect on the protein includes:
o chemical
catalytic activity is often lost
o physical
solubility is decreased
o biological
function is lost
Agents which cause denaturation
• Heat:
o increase the kinetic energy of the protein
o there are weak side chain interactions which can be disrupted because of the increased thermal energy of vibration
o in general temperature above 50 or 60 degrees will denature most proteins:
• melt temperature
• Mechanical Action:
o caused by stretching
o this decreases solubility
• Detergents:
o surface acting agents
o disrupts hydrophobic interactions found in the protein chain
• Organic Chemicals:
o polar solvents such as acetone and alcohols
• competes for the hydrogen bonds found in the original 3 – D structure
• breaks up the internal hydrogen bonds
o this twists and unwinds the chain
o –HN- group forms hydrogen bonds with –C=O of an acetone molecule
o an –HN- form hydrogen bonds with HO- of an alcohol
• pH change:
o Excess hydrogen ions or hydroxyl groups interact with the basic or acidic side groups and disrupt the salt bridges creating their own acid/base relationships
o also disrupts hydrogen bonds
o exposure to strong acids and bases for a long period of time will result in the hydrolysis of the protein chain
• Inorganic salts
o PbCl2
o AgCl
o HgCl2
• reducing agents
o high concentrations of heavy metals can disrupt salt bridges
o bind w/ sulfur contain groups to create metal sulfides
• Oxidizing reagents:
o create sulfur bridges
o HNO3
• Alaloidal reagents
o disrupt salt bridges
o disrupt hydrogen bonds
• if the changes in the structure is small, denaturation can be reversed and the protein can resume its secondary and tertiary structure and biological function
• in biological systems, certain proteins called chaperones help a newly synthesized polypeptide chain to assume the proper secondary and tertiary structure that are necessary for the functioning of that molecule and prevent foldings that are not biologically active
Wednesday, June 16, 2004
carbohydrates
Carbohydrates
Section: 22.1
• carbohydrates: a member of a large class of naturally occurring polyhydroxy aldehydes or ketones
name of compd. ends w/ the “ose” ending
• monosaccharides: a carbohydrate that can not be broken down into smaller units by hydrolysis with aqueous acid
o typically three to seven carbons in length
glucose: pentylhydroxylhexanal
fructose: pentylhydroxylhexanone
galactose: penthylhyroxylhexanal
page 630
• disaccharide: a carbohydrate, which yields two monosaccharides on hydrolysis, identical or different. Bonds are really ether like linkages (glycosidic bonds) page 647 - 649
o held together by a glycosidic bond or also called acetal bond
lactose
maltose
sucrose
• polysaccharides: a carbohydrate that is composed of many monosaccharides bonded together. This is really a polymer of many monosaccharides put together end to end. Really a polymer of monosaccharides. Monomer composition cab be identical or different, and if different order determines the type polysaccharide
o complex carbohydrates: page 653
glycogen: animal
cellulose: plant: fiber
amylose: plant
amylopectin: plant
• aldose: monosaccharide which contains an aldehyde functional group: page 630
• ketose: a monosaccharide which contains a ketone functional group
Naming and Examples of monosaccharides
• the number of carbons is specified by multiplicative prefixes identical to that in naming other compds
• see page: 630
• can you find the aldehyde functional group?
• can you find the ketone functional group?
Section 22.2 Handedness of Carbohydrates
• the simplest of the carbohydrates is the three carbon compd. Glyceraldehydes:
o page 631
• there exists two forms:
o D-glyceraldehyde
o L-glyceraldehyde
• these compds exist chiral character
o meaning lack of plane of symmetry
o they are mirror images of each other
o same chemical properties
o all physical properties are the same except their ability to rotate a plane of polarized light
o there are called optical isomers
o the measurement of optical rotations is accomplished by a device called a polarimeter
o one will rotate light to the right and the other will rotate light to the left
o this compd. w/ one chiral center can only have two optical isomers
o if there are more chiral centers, then there are more optical isomers possibilities
o if you have 2 chiral centers, then you can have four optical isomers
two optical isomer pairs
o thus there is a D and L erythrose and a D and L threose
o however, erythrose and threose are stereoisomerisms
stereoisomers: some formula and connections but different spatial arrangement
diastereomers: stereoisomers that non mirror images of each other
Section 22.3 Fisher Projections
D-sugars: monosaccharides with the OH group on the chiral atom farthest from the carbonyl group pointing to the right in a
Fisher projection. The representation “dextro” is derived from the fact that the OH group points to the right
L-sugar: monosaccharide with the OH group on the chiral atom farthest from the carbonyl group pointing to the left in a Fisher projection. The representation “levo” is derived from the fact the OH group points to the left
• see page 635
In a Fisher projection, the carbonyl group of the ketone or the aldehyde is always placed at the top of the projection
glyceraldehyde is the simplest of the monosaccharides
this means that the OH and the H groups pointing to the left and the
right of the chiral atoms are projecting out of the paper and those above and below the chiral centers are projecting into the paper
see page 633 again
note in the D sugar form the OH group projects out of the paper
and to the right
note in the L sugar form the OH group projects out of the paper and
to the left
22.4 Structure of Glucose and others
• sometimes call dextrose or blood sugar
• source of energy for almost all living organisms
• stored as a polymer as starch in plants and glycogen in animals
• hemiacetal forms from the internal condensation of an aldehyde group and an alcohol group of that sugar
• internal hemiacetal formation is possible
• the C1 and C5 carbons condense to form a six member ring which has an oxygen in the ring instead of a carbon
• see figure 22.3 page 637
• OH groups pointing left point up in the cyclic structure and those which point to the right, point down
• the hemiacetal carbon is always bonded to two oxygen atoms
• this means that the carbon is chiral
• this creates alpha and beta anomers
• in the beta form the OH group points up and in the alpha form the OH group points down
• anomers: cyclic sugars that differ only in the positions of the OH on the hemiacetal carbon; the alpha form has the OH group on the opposite side of the –CH2OH; the beta form has the –OH group on the same side as the –CH2OH
• anomeric carbon: the hemiacetal C atom in the cyclic sugar, the C atom bonded to an –OH group and an O in the ring
o in aldoses it is carbon # 1
o in ketone based sugars it is carbon # 2 page 643
• mutarotation: change in rotation of plane polarized light resulting form the equilibrium between cyclic anomers and the open chain form of a sugar
• see page 638 for review: KNOW!
• Bullet points page 639
Section 22.5: Important Monosaccharides
• the monosaccharides w/ their many hydroxyl groups which permit hydrogen bonding between other monosaccharides are generally high melting, white crystalline solids
• w/ many opportunities for hydrogen bonding, they have high solubility in water and are insoluble in non-polar solvents
• most are sweet in taste and digestible as an energy source
• those of interest include:
o glyceraldehyde
o fructose
o aldohexoses
o aldopentoses
• most are in the D-family
• Glucose:
o most important of the carbohydrate of human metabolism
o one of the final products of carbohydrate digestion
o provides acetyl groups in the form of acetyl-SCoA for the Krebs’ Cycle
o hormones insulin and glucagon maintain proper glucose levels in the blood
• Galactose:
o component of the digestion of lactose
o aldohexose (see page 648)
o identical in arrangement of the carbons and hydroxyl groups in order, but orientation of the OH- group at position turned and opposed to glucose where it is turned down
o the body converts galactose to glucose
o galactose can be made from glucose to provide lactose for breast milk
o galactosemia: genetic disorder which the individual cannot process galactose, its build up may cause mental retardation, liver failure, and cataracts
• Fructose:
o see page 643
o ketohexose
o part of the glycolysis cycle
o six carbon sugar
o because of the presence of the ketone functional group and through internal condensation with carbon # 5, a five member ring results
o there are also α and β anomers
o sweeter then sucrose
• Ribose and 2-Deoxyribose
o see page 644
o both are five carbon aldehyde sugars
o found in many aspects of biological chemistry, especially DNA, RNA, and cyclic AMP
22.6 Reactions of Monosaccharides
• Reactions w/ oxidizing agents: Reducing sugars by definition
o aldehydes can be oxidized to carboxylic acids, but that reaction applies only to open chained form of the aldose monosaccharides
o if you have a given sample, the open chain will continue to react with the oxidizing agent, the equilibrium will shift, until all of the cyclic forms are consumed
o any carbohydrate that reacts w/ a reducing agent is called a reducing sugar by definition
o a ketose also behave as reducing sugar in basic solution such as Benedicts’ because of a keto-enol tautomeric shift, that is the ketone is converted to an aldehyde
o this aldehyde then can undergo oxidation
o in basic solns., all monosaccharides of either ketose or aldose origin behave as reducing sugars
• Reactions with Alcohols:
o an alcohols is a hemiacetal which can react with other alcohols to make a acetal
o a acetal has two OR groups bonded to the same carbon
o the class of compounds which reacts when a cyclic hemiacetal reacts together is called a glycoside:
a cyclic acetal formed by the Rx of a monosaccharide with an alcohol w/ accompanied by the release of water, a condensation reaction
• the bond which o=is formed by this condensation reaction is called a glycosidic bond, by definition, the anomeric carbon must be involved in that bond
• when two monosaccharides are combined, the anomeric carbon of one carbon is reacted w/ the –OH of another monosaccharide
22.7 Disaccharides:
• when you have a disaccharide, the bond can also be α or β
• in the example on page 647 there is representation of an α and β bond types. These are stereoisomers of each other
• Maltose:
o malt sugar
o two α D-glucose molecules are linked in an alpha configuration
o note that carbons 1 and 4 are involved, hence name is called α 1-4 glycosidic bond
• Lactose:
o β-D-Galactose
o β-D-Glucose
o β-1,4 glycosidic bond
o age increases risk of lactose intolerance
• Sucrose:
o table sugar
o hydrolysis of sucrose produces:
α-D-glucose
β-D-fructose
• called invert sugar
• non reducing sugar because the anomeric carbons are linked together
• bond type is a 1,2 anomeric link
• can not ID as α or β link because both anomeric carbons are joined together
• only common disaccharide which is not a reducing sugar, a good ID for lab when trying to distinguish between two disaccharides
22.8 Variation on Carbohydrate Theme
• monosaccharides w/ modified functional groups are found and have many important structural applications, see page 651
• Chitin:
o structural polymer
o insect shells
o N-acetyl-D-glucosoamine
• Connective tissue Polysaccharides:
o protein fibers are embedded in a matrix of un-branched polysaccharides (mucopolysaccharides)
o these gel like polymers behave as lubricants
o repeating unit of two modified monosaccharides
Hyaluronate: 25K units in length
rigid material
holds water
synovial fluid
• Chrondroitin-6-sulfate:
o tendons and cartilage
o linked to proteins
o dietary supplements
• Heparin:
o another polymer
o anticoagulant
o various composition contain sulfate groups
o has many negative charges to bond tightly to blood clotting factors
• Glycoproteins:
o a protein that’s a short carbohydrate chain
o carbohydrate is connected to the protein by a glycosidic bond between the anomeric carbon and a side chain of the protein, the bond is of two types, a C-N glycosidic bond or C-O glycosidic bond to an oxygen atom of a side chained hydroxyl group
o major function is cell surface markers
o important in blood group identification
o the protein portion is buried in the cell membrane and the carbohydrate portion extends above the surface of the cell membrane
o see page 654
o note the common N-acetyl-D-glucose amine bade for all three blood groups
o L-fucose is found in all three blood groups
o N-acetyl-D-galactose amine is found only in blood group A
o D-galactose is found only in blood group B
o if you are an AB individual, then you have the separate glycoproteins which contain N-acetyl-galactose amine and galactose as your markers
22.9 Important Polysaccharides
• Cellulose:
o see page 653
o fibrous structure that provides support in plants
o made up of β-D-glucose units in repeated fashion
o links are called β 1-4 glycosidic bonds
o see anti-parallel arrangement
o hydrogen bonding holds the structure together
o we as humans can not digest cellulose because we lack the enzyme β-cellulase
• Starch:
o General properties
polymer of α-D-glucose
joined by α 1-4 glycosidic links
fully digestible because α-amylase
found only in plant material:
• beans
• potato
• wheat
• rice
o amylose: page 656
20% of the total plant starch
somewhat soluble in hot water
several hundred to 1000 units of α-D-glucose linked together by α 1-4 glycosidic bonds
coils in helical arrangement, not anti-parallel sheets
w/o branching
o amylopectin: page 656
80 % of the starch
identical monomer construction
up to 100,000 monomer units
α 1-6 branch to an α-D-glucose occurs approximately on each 25th α-D-glucose unit, branches can also be 100,000 units long
digested in small intestine by α-amylase which catalyzes the α 1-4 links
o Glycogen:
animal starch
energy storage in the liver and muscles
when used as energy source, the glucose is converted to glucose-6-phosphate for glycolysis
branch points as in amylopectin but every 10 units
size is 1,000,000 units
readily mobilized form of glucose storage
designed to increase the amount of glucose that is immediately available following between meals
important for blood glucose levels and regulation
reservoir of glucose for strenuous muscle activity
the α 1-6 branch is broken down by a debranching enzyme called α 1-6 gluosidase which is found in the liver
other debrancing enzymes, collectively called pancreatins complete the activity in the small intestine
carbohydrates
Carbohydrates
Section: 22.1
• carbohydrates: a member of a large class of naturally occurring polyhydroxy aldehydes or ketones
name of compd. ends w/ the “ose” ending
• monosaccharides: a carbohydrate that can not be broken down into smaller units by hydrolysis with aqueous acid
o typically three to seven carbons in length
glucose: pentylhydroxylhexanal
fructose: pentylhydroxylhexanone
galactose: penthylhyroxylhexanal
page 630
• disaccharide: a carbohydrate, which yields two monosaccharides on hydrolysis, identical or different. Bonds are really ether like linkages (glycosidic bonds) page 647 - 649
o held together by a glycosidic bond or also called acetal bond
lactose
maltose
sucrose
• polysaccharides: a carbohydrate that is composed of many monosaccharides bonded together. This is really a polymer of many monosaccharides put together end to end. Really a polymer of monosaccharides. Monomer composition cab be identical or different, and if different order determines the type polysaccharide
o complex carbohydrates: page 653
glycogen: animal
cellulose: plant: fiber
amylose: plant
amylopectin: plant
• aldose: monosaccharide which contains an aldehyde functional group: page 630
• ketose: a monosaccharide which contains a ketone functional group
Naming and Examples of monosaccharides
• the number of carbons is specified by multiplicative prefixes identical to that in naming other compds
• see page: 630
• can you find the aldehyde functional group?
• can you find the ketone functional group?
Section 22.2 Handedness of Carbohydrates
• the simplest of the carbohydrates is the three carbon compd. Glyceraldehydes:
o page 631
• there exists two forms:
o D-glyceraldehyde
o L-glyceraldehyde
• these compds exist chiral character
o meaning lack of plane of symmetry
o they are mirror images of each other
o same chemical properties
o all physical properties are the same except their ability to rotate a plane of polarized light
o there are called optical isomers
o the measurement of optical rotations is accomplished by a device called a polarimeter
o one will rotate light to the right and the other will rotate light to the left
o this compd. w/ one chiral center can only have two optical isomers
o if there are more chiral centers, then there are more optical isomers possibilities
o if you have 2 chiral centers, then you can have four optical isomers
two optical isomer pairs
o thus there is a D and L erythrose and a D and L threose
o however, erythrose and threose are stereoisomerisms
stereoisomers: some formula and connections but different spatial arrangement
diastereomers: stereoisomers that non mirror images of each other
Section 22.3 Fisher Projections
D-sugars: monosaccharides with the OH group on the chiral atom farthest from the carbonyl group pointing to the right in a
Fisher projection. The representation “dextro” is derived from the fact that the OH group points to the right
L-sugar: monosaccharide with the OH group on the chiral atom farthest from the carbonyl group pointing to the left in a Fisher projection. The representation “levo” is derived from the fact the OH group points to the left
• see page 635
In a Fisher projection, the carbonyl group of the ketone or the aldehyde is always placed at the top of the projection
glyceraldehyde is the simplest of the monosaccharides
this means that the OH and the H groups pointing to the left and the
right of the chiral atoms are projecting out of the paper and those above and below the chiral centers are projecting into the paper
see page 633 again
note in the D sugar form the OH group projects out of the paper
and to the right
note in the L sugar form the OH group projects out of the paper and
to the left
22.4 Structure of Glucose and others
• sometimes call dextrose or blood sugar
• source of energy for almost all living organisms
• stored as a polymer as starch in plants and glycogen in animals
• hemiacetal forms from the internal condensation of an aldehyde group and an alcohol group of that sugar
• internal hemiacetal formation is possible
• the C1 and C5 carbons condense to form a six member ring which has an oxygen in the ring instead of a carbon
• see figure 22.3 page 637
• OH groups pointing left point up in the cyclic structure and those which point to the right, point down
• the hemiacetal carbon is always bonded to two oxygen atoms
• this means that the carbon is chiral
• this creates alpha and beta anomers
• in the beta form the OH group points up and in the alpha form the OH group points down
• anomers: cyclic sugars that differ only in the positions of the OH on the hemiacetal carbon; the alpha form has the OH group on the opposite side of the –CH2OH; the beta form has the –OH group on the same side as the –CH2OH
• anomeric carbon: the hemiacetal C atom in the cyclic sugar, the C atom bonded to an –OH group and an O in the ring
o in aldoses it is carbon # 1
o in ketone based sugars it is carbon # 2 page 643
• mutarotation: change in rotation of plane polarized light resulting form the equilibrium between cyclic anomers and the open chain form of a sugar
• see page 638 for review: KNOW!
• Bullet points page 639
Section 22.5: Important Monosaccharides
• the monosaccharides w/ their many hydroxyl groups which permit hydrogen bonding between other monosaccharides are generally high melting, white crystalline solids
• w/ many opportunities for hydrogen bonding, they have high solubility in water and are insoluble in non-polar solvents
• most are sweet in taste and digestible as an energy source
• those of interest include:
o glyceraldehyde
o fructose
o aldohexoses
o aldopentoses
• most are in the D-family
• Glucose:
o most important of the carbohydrate of human metabolism
o one of the final products of carbohydrate digestion
o provides acetyl groups in the form of acetyl-SCoA for the Krebs’ Cycle
o hormones insulin and glucagon maintain proper glucose levels in the blood
• Galactose:
o component of the digestion of lactose
o aldohexose (see page 648)
o identical in arrangement of the carbons and hydroxyl groups in order, but orientation of the OH- group at position turned and opposed to glucose where it is turned down
o the body converts galactose to glucose
o galactose can be made from glucose to provide lactose for breast milk
o galactosemia: genetic disorder which the individual cannot process galactose, its build up may cause mental retardation, liver failure, and cataracts
• Fructose:
o see page 643
o ketohexose
o part of the glycolysis cycle
o six carbon sugar
o because of the presence of the ketone functional group and through internal condensation with carbon # 5, a five member ring results
o there are also α and β anomers
o sweeter then sucrose
• Ribose and 2-Deoxyribose
o see page 644
o both are five carbon aldehyde sugars
o found in many aspects of biological chemistry, especially DNA, RNA, and cyclic AMP
22.6 Reactions of Monosaccharides
• Reactions w/ oxidizing agents: Reducing sugars by definition
o aldehydes can be oxidized to carboxylic acids, but that reaction applies only to open chained form of the aldose monosaccharides
o if you have a given sample, the open chain will continue to react with the oxidizing agent, the equilibrium will shift, until all of the cyclic forms are consumed
o any carbohydrate that reacts w/ a reducing agent is called a reducing sugar by definition
o a ketose also behave as reducing sugar in basic solution such as Benedicts’ because of a keto-enol tautomeric shift, that is the ketone is converted to an aldehyde
o this aldehyde then can undergo oxidation
o in basic solns., all monosaccharides of either ketose or aldose origin behave as reducing sugars
• Reactions with Alcohols:
o an alcohols is a hemiacetal which can react with other alcohols to make a acetal
o a acetal has two OR groups bonded to the same carbon
o the class of compounds which reacts when a cyclic hemiacetal reacts together is called a glycoside:
a cyclic acetal formed by the Rx of a monosaccharide with an alcohol w/ accompanied by the release of water, a condensation reaction
• the bond which o=is formed by this condensation reaction is called a glycosidic bond, by definition, the anomeric carbon must be involved in that bond
• when two monosaccharides are combined, the anomeric carbon of one carbon is reacted w/ the –OH of another monosaccharide
22.7 Disaccharides:
• when you have a disaccharide, the bond can also be α or β
• in the example on page 647 there is representation of an α and β bond types. These are stereoisomers of each other
• Maltose:
o malt sugar
o two α D-glucose molecules are linked in an alpha configuration
o note that carbons 1 and 4 are involved, hence name is called α 1-4 glycosidic bond
• Lactose:
o β-D-Galactose
o β-D-Glucose
o β-1,4 glycosidic bond
o age increases risk of lactose intolerance
• Sucrose:
o table sugar
o hydrolysis of sucrose produces:
α-D-glucose
β-D-fructose
• called invert sugar
• non reducing sugar because the anomeric carbons are linked together
• bond type is a 1,2 anomeric link
• can not ID as α or β link because both anomeric carbons are joined together
• only common disaccharide which is not a reducing sugar, a good ID for lab when trying to distinguish between two disaccharides
22.8 Variation on Carbohydrate Theme
• monosaccharides w/ modified functional groups are found and have many important structural applications, see page 651
• Chitin:
o structural polymer
o insect shells
o N-acetyl-D-glucosoamine
• Connective tissue Polysaccharides:
o protein fibers are embedded in a matrix of un-branched polysaccharides (mucopolysaccharides)
o these gel like polymers behave as lubricants
o repeating unit of two modified monosaccharides
Hyaluronate: 25K units in length
rigid material
holds water
synovial fluid
• Chrondroitin-6-sulfate:
o tendons and cartilage
o linked to proteins
o dietary supplements
• Heparin:
o another polymer
o anticoagulant
o various composition contain sulfate groups
o has many negative charges to bond tightly to blood clotting factors
• Glycoproteins:
o a protein that’s a short carbohydrate chain
o carbohydrate is connected to the protein by a glycosidic bond between the anomeric carbon and a side chain of the protein, the bond is of two types, a C-N glycosidic bond or C-O glycosidic bond to an oxygen atom of a side chained hydroxyl group
o major function is cell surface markers
o important in blood group identification
o the protein portion is buried in the cell membrane and the carbohydrate portion extends above the surface of the cell membrane
o see page 654
o note the common N-acetyl-D-glucose amine bade for all three blood groups
o L-fucose is found in all three blood groups
o N-acetyl-D-galactose amine is found only in blood group A
o D-galactose is found only in blood group B
o if you are an AB individual, then you have the separate glycoproteins which contain N-acetyl-galactose amine and galactose as your markers
22.9 Important Polysaccharides
• Cellulose:
o see page 653
o fibrous structure that provides support in plants
o made up of β-D-glucose units in repeated fashion
o links are called β 1-4 glycosidic bonds
o see anti-parallel arrangement
o hydrogen bonding holds the structure together
o we as humans can not digest cellulose because we lack the enzyme β-cellulase
• Starch:
o General properties
polymer of α-D-glucose
joined by α 1-4 glycosidic links
fully digestible because α-amylase
found only in plant material:
• beans
• potato
• wheat
• rice
o amylose: page 656
20% of the total plant starch
somewhat soluble in hot water
several hundred to 1000 units of α-D-glucose linked together by α 1-4 glycosidic bonds
coils in helical arrangement, not anti-parallel sheets
w/o branching
o amylopectin: page 656
80 % of the starch
identical monomer construction
up to 100,000 monomer units
α 1-6 branch to an α-D-glucose occurs approximately on each 25th α-D-glucose unit, branches can also be 100,000 units long
digested in small intestine by α-amylase which catalyzes the α 1-4 links
o Glycogen:
animal starch
energy storage in the liver and muscles
when used as energy source, the glucose is converted to glucose-6-phosphate for glycolysis
branch points as in amylopectin but every 10 units
size is 1,000,000 units
readily mobilized form of glucose storage
designed to increase the amount of glucose that is immediately available following between meals
important for blood glucose levels and regulation
reservoir of glucose for strenuous muscle activity
the α 1-6 branch is broken down by a debranching enzyme called α 1-6 gluosidase which is found in the liver
other debrancing enzymes, collectively called pancreatins complete the activity in the small intestine
enzymes
Enzymes
catalyst: defined as a substance which speeds up a chemical
reaction w/o being consumed in the process.
1) Can be inorganic or organic in nature.
2) do not change the position of the equilibrium, only the activation energy hill for that particular reaction to occur.
3) cannot make a reaction occur which would not normally occur, albeit, slowly
catalyzed reactions have three components:
1). reactants or substrates
2). catalysts
3). products
enzymes: an organic molecule, frequently protein in nature
which acts as a biological catalyst. Those, which are
not protein in nature, which are similar to RNA
molecules are called ribozymes
complexity: how they are put together; most enzymes are
put together
1) made up of many amino acids sequenced in a particular order, primary structure
a. also non protein components are also present
i. metals
ii. vitamins
2) with a defined 3- structure
3) Inorganic catalysts can be complex, but are not made up of amino acids.
4) W/o this unique 3-D arrangement, the conversion of reactant to product will not occur.
insert chart
specificity: the limitation of the activity of an enzyme to a specific substrate, specific reaction, or a specific type of reaction
1) Sometimes there is one enzyme for an individual substrate; glucose-6-phosphorylase
2) other times, the enzyme can act on a class of molecules or specific functional groups:
3) reductase:
a) aldehydes primary alcohols
b) ketones secondary alcohol
c) double bonds single bonds by the addition of hydrogen in the form of NADH, H+
4) most work only on L-amino acid enantiomers, left handed amino acid; a left handed enzyme active site
5) lipases only triglycerides
6) pepsin , trypsin, carboxypeptidase only proteins
7) urease urea and no other amides
8) pancreatin glycogen, amylose, amylopectin
9) DNA polymerase responsible for adding nucleotides to the growing DNA chain in the 5’ to the 3’ direction
10) peptidyl synthetase adds the amino acids to the growing polypeptide chain on the ribosome
11) translocase moves mRNA across the ribosome one triplet at a time
12) RNA nuclease destroys un-needed RNA
turnover number: the catalytic activity of an enzyme under
defined in vivo conditions: See chart page 543
1) Taken at enzyme saturation:
a. concentrations of enzymes and substrates are predetermined for that assay
2) all cofactors need to be present
3) defined pH
4) defined temp
5) Turn over number varies with the enzyme:
a. some are very fast:
i. carbonic anhydrase
a. found in the blood responsible for the pH balance of carbon dioxide in the blood
b. needs to be fast because of the constant production of carbon dioxide because of catabolism,
c. if was not fast, acidosis would occur
b. some are very slow because of high specificity
i. DNA polymerase, which is required for replicating DNA molecule
a. slow is good, because it allows for high fidelity for the replication of the DNA molecule.
Enzyme Structure
1) Enzymes are frequently in globular shape, having complex 3-D structures, which make them soluble in water, logical since most biochemical reactions are water based
2) components of an enzyme:
a. cofactor: a small non-protein part of an enzyme that is essential for the functioning of the enzyme. Cofactors bring about unique 3-D affects at the active site to permit the conversion of the reactant or substrate to product. Held tightly to the enzyme by:
a. temporary covalent bonds
b. hydrogen bonds
c. hydrophobic bonds
2. metals: bind with lone electron pairs;
i. called trace metals
ii. Cr
iii. Zn
iv. Co
v. Fe
vi. Ni
vii. Mn
viii. Mg
ix. Va
x. Mo
xi. Se
3. coenzyme: small organic molecule such that provide reactive groups in the active site which would not normally be present in the R groups of the amino acids of the primary sequence:
i. NAD
ii. NADH
iii. NADP
iv. NADPH
v. FAD
vi. FADH2
apoenzyme: the protein component of the enzyme
holoenzyme: the combination of the apoenzyme and cofactor/s.
It is possible for both metals and other organic
non-protein components to be present at the same
time. This combination required for biological
activity of the enzyme
key: the apoenzyme or the cofactors alone can not catalyze the
reaction. Both are needed for the catalytic event to occur
Enzyme Nomenclature
• every name of an enzyme has two parts:
o first part describes the substrate the enzyme acts on
o second part defines the enzyme class
• if the enzyme has a name like ALCOHOL dehydrogenase, this is really a oxidase type enzyme which will work on a general class of compounds such as primary and secondary alcohols to remove hydrogens.
o induced fit enzyme
o NAD+ NADH, H+
o primary alcohol = aldehyde
o secondary alcohol ketone
• if the enzyme is called ethanol dehydrogenase, then the enzyme is specific for ethanol:
o lock and key fit enzyme
Enzymes Reaction Classification
1) Enzymes are divided into six main classes according to the general kinds of reactions that they catalyze, and each class is then additionally divide
a). oxidoreductases: catalyze oxidation and reduction reactions, which may involve the addition or removal of oxygen or hydrogen. These redox reactions; Typically involve coenzyme NAD+, NADH, NADP+, and NADPH
CH3-CH2-OH + NAD+ < ===== CH3-C-H + NADH, H+
||
O
• Description of the events: ethanol is oxidized to ethanal by the removal of two hydrogens. NAD+ is reduced when two hydrogens are added to the coenzyme creating a reduced coenzyme with the following formuli: NADH,H+. Sometimes the author writes it as NADH, both are considered acceptable
a) transferases: catalyze the transfer of a group from one molecule to another. Typical in the deamination and amination of amino acids
b) Hydrolyases: catalyzes the hydrolysis of substrates the breaking of bonds w/ the addition of water. The digestion of carbohydrates and proteins are good examples:
i. carbohydratases
1. lactase
2. maltase
3. sucrase
4. pancreatin
5. amylase
ii. peptidases
1. trypsin
2. pepsin
d) isomerase: catalyzes the isomerization (rearrangement of atoms) of a substance in reactions that have but only one substrate and one product
DHAP ===G3P
G6P === F6P
e) lyases: catalyze the addition of a molecule such as water, carbon dioxide, and ammonia to a double bond or the reverse reaction, in which a molecule is
eliminated to leave a double bond. Note this does not include hydrogen. The removal of two hydrogens is a dehydrogenase reaction. The reaction below is catalyzed by fumarase.
fumarate + H2O L-malate
f) ligases: catalyzes the bonding together of two substrate molecules. They are usually tied to the hydrolysis of ATP ADP and P which provides the energy for this condensation reaction. Typical reactions include:
1. building of polysaccharides
2. building of polypeptides
Enzymes Mode of Action
• enzyme mechanics are predicated on two fundamental ideas:
why enzymes are so specific
how enzymes lower the activation energy
• making G favorable
• specificity is linked to the activity about the active site of the enzyme; because the active site provides:
a) the right environment for the reaction
b) has “R” groups which hold the substrate to the active site by non-covalent interactions and temporary covalent bonds; which could include
salt bridges
hydrogen bonds
hydrophobic interactions
c) has the right groups needed for the catalytic event
• Two modes of explaining the activity of enzymes reside in the following models:
lock and key
induced fit
• Lock and Key Model:
the first model
resembles idea of lock and key
implies that the enzyme are rigid structures
one substrate and one enzyme, absolute specificity
restrictive
• Induced Fit Model:
Daniel Kichland
second model
enzymes molecules not rigid structures
accounts for changes in the actives site to accommodate other substrates and to facilitate the catalytic event
shape of active site modified to accommodate the substrate
the non active site of the enzyme surrounds the active site once the substrate has entered
accounts for the fact that there are constant motions in both the substrate and the enzyme
• The purpose of the active site:
many organic reactions require acid groups, basic groups, or metal ions
the active site can provide these groups in the form of the “R” groups without disrupting the pH environment of the body fluids
also provides a region for the cofactors to do their work
• Events at the active site:
first the substrate must be drawn into the active site by some non covalent forces to form and enzyme substrate complex (ES)
the substrate when it is bound to the active site is twisted and turned so it is in a higher energy state, this lowers the activation energy
bond re-arrangement occurs between the substrate and the active site
then the product is release
also any cofactors which participated are also released
• enzymes act as catalysts because of the following:
o bring substrate(s) and catalytic sited close together; this is called the proximity effect
o hold the substrate(s) at the exact distance and in the proper orientation necessary for the Rx to occur, this is called the orientation effect
o provide acidic, basic, hydrophobic, and polar groups required for catalysis, this is called the catalytic effect
o lower the activation barrier by inducing strain, twisting and turning in the substrate molecule, this is called the energy effect
All enzyme reactions are defined in the following general way
Enzyme + substrate = [ES] = Enzyme + Product
Conditions which affect the behavior of Enzymes
• normally an increase in temperature will increase the rate of most chemical reactions, enzyme catalyzed reactions are no exception, but these do not increase continuously
• the rate will reach a maximum and then will continue to decline w/ rising temperature
• this is because the enzyme will start to denature as the temp. is increased to much because of the disruption of the non-covalent forces which hold the enzyme together start to break apart as the kinetic energy of the molecule is increased
• this is because protein conformations are sensitive to temperatures and pH
• this disrupts the active site, so the substrate might not fit properly, thereby decreasing the turnover rate, page 553
• most enzymes denature and lose their catalytic activity above 50 – 60 deg C.
• however, the bacteria in the hydrothermal events can withstand temperatures in excess of 460 deg F
• cooling opt temp. will not cause the enzyme to denature
• small increases above opt. temp. and then decrease, may allow the enzyme to recover
• thus. opt temp. is really a balance between maximum catalytic activity and the increased risk of denaturing the enzyme
insert temp chart page 553
The effect of pH
• since the pH of the environment changes the conformation of the protein, it is natural to except similar affects on rate
• each enzyme operates best at certain pH:
o pepsin 1.5 – 2.5
o salivary amylase 6.6 – 6.8
o trypsin 8.0 – 10.0
• again, within a narrow pH region is enzyme is maximally active
• at extreme pH changes, the enzyme is irreversibly denatured
• most enzymes are capable of working within a 5 – 9 pH range and outside this range, they will denature
• see figure 19.5 B
Effect of [Enzyme] and [Substrate] on Enzyme Activity
• if the [substrate] is held constant and the [enzyme] is increased, the turnover number will increase linearly
if [enzyme] x 2 x 2
if [enzyme] x 3 x 3
this is called a direct proportion
not true of most enzyme reactions because in general the [enzyme] [substrate]
means that the enzyme is saturated with substrate
see figure 19.6 A
• if [substrate] varied with a fixed [enzyme]
o see figure 19.6 B
o rate w/ increase [substrate]
o when enzyme becomes saturated, rate levels off
this is called zero order kinetics because the graph runs parallel to the x-axis at saturation of the enzyme
o turnover number determined by how fast the ES complex is converted to product
o at this point, increase [substrate] has not affect
o increasing [substrate] is no longer effective because the excess substrate can not find any active sites to attach to because the enzyme is now saturated
• normally the enzyme is rarely saturated and determined by the efficiency in two ways because of the quick removal of the product which creates constant openings at the active site
how fast ES forms
how fast ES product
• max efficiency of enzyme is between 108 and 109 collisions per second:
triose phosphate isomerase
catalase
Enzyme Regulation: Feedback and Allosteric Control
• enzyme are often regulated by environmental conditions, this is the relationship of one product from one enzyme pathway, how it affects another
• remember that biological reaction pathways are dependent upon a series of consecutive reactions in which the product of one reaction is the reactant for the next one
P1 == P2 == P3 == P4
• each step is catalyzed by a different enzyme; the last product P4 might inhibit the enzyme for the conversion of P1 to P2
• if the concentration of needed P4 is low, the three steps proceed rapidly
• when P4 concentration builds, the three pathways are inhibited
• this is feedback; regulation of an enzymes activity by the product of a reaction later in a series of pathways
• in essence, all enzymes pathways must be regulated
• basic strategies of regulation:
o activation any process that initiates an increase in the action of an enzyme
o inhibition any process that slows or stops the action of an enzyme
• feedback control often occurs by allosteric control; which is the binding of a regulator at one site on the enzyme which affects the binding of the another molecule at another different site
• most allosteric enzymes have more then one protein chain, multiple active sites, and two kinds of binding sites for regulators:
activators
inhibitors
advantage: regulators need not resemble the substrate and prematurely behave as a competitive inhibitor
advantage: allows for fine level of control
• binding of the regulator changes the active site, and its availability for the substrate
• allosteric enzymes are sensitive to the presence of inhibitors and activators
• often the rate limiting enzymes in a series of enzymatic reactions
Enzyme Regulation: Inhibition
• inhibition can be classified as being:
reversible
irreversible
• inhibition can be classified as being:
competitive
non competitive
• Noncompetitive Inhibition: enzyme regulation in which an inhibitor binds to the enzyme elsewhere than the active site, changing the shape of the enzyme’s active site and reducing the enzyme’s efficiency
• this means that the inhibitor does not compete for the active site, and therefore does not resemble the substrate
see figure 19.8 page 556
really a form of allosteric control by definition
this is a form of reversible inhibition
presence of the inhibitor lowers maximum rate because the active site less accessible
rate will increase with increasing substrate concentration, but will be limited to lower levels until the inhibitor is removed
max rate decreased in the presence of a non competitive inhibitor because the enzyme can not bind the substrate as well because of changes in the 3-D configuration which affects the accessibility of the incoming substrate for the active site
Competitive Inhibition
• competitive inhibition: enzyme reaction in which an inhibitor competes with a substrate for binding to the active site. A reversible process.
• see Figure 19.8 b
• explained by both the lock and key and the induced fit model of substrate binding to the active site
• the inhibitor molecules fits into the active site the way that the normal substrate molecule
• thus it is an imposter, limiting access of the normal substrate for the active site and the enzyme would be tied up
• a competitive inhibitor reversibility binds to the active site through normal active site-substrate bonding. Might want to call it an EI complex, and the rate of the enzyme is affected by how quickly the EI == E and I
• how much affect the inhibitor affects the process is determined by the [inhibitor] relative to the [substrate]
o how much inhibitor is present relative to the concentration of the enzyme
o how much affinity the inhibitor has for the active site
o this means if the active site “prefers” the inhibitor over the incoming substrate, then the inhibitor will be the determining factor in rate of the reaction with the respect to the substrate itself
• max turnover of the enzyme can be achieved by the addition of move substrate molecules provided that you do not increase the concentration of the inhibitor, however, how long to get to max turnover number is dependent upon the [inhibitor] and the affinity that the inhibitor has for the active site of the enzyme
• the enzyme achieve max rate very quickly w/o the presence of the inhibitor. see figure 19.8 b
• often used in treating methanol poisoning
• ethanol is competitive inhibitor of the methanol dehydrogenase enzyme which methanol to ethanal,
Irreversible Inhibition
• irreversible inhibition: enzyme deactivation in which an inhibitor forms covalent bonds to the active site, permanently blocking access to the site
• this is by definition not denaturing the enzyme, even though denaturing could result
• the enzyme can not return to an active state
• many irreversible inhibitors are poisons which can include the following heavy metals:
Hg2+
Pb2+
form covalent bonds to sulfur contain AAs
• can not return the enzyme to its normal max turn over number by increase [substrate] or reduce [inhibitor]
• once the inhibitor binds, then it is illogical to think that you can decrease its concentration since it does not reversibly move in and out of the active site
• enzyme must replaced
Chemical messengers
Chapter 20 Chemical Messengers
Section: 20.1 Messengers Molecules
• this is what is called process control
• chemical messengers control most of the bodies functions
• can be carried by blood stream or by action of nerve cells
• all interaction depends on a target which has a specific receptor:
o receptor: a molecule or a portion of a molecule which either a hormone or a neurotransmitter, or some other biologically active molecule connects to initiate a response; activation or inhibition
o hormone: a chemical messenger secreted by the endocrine system and transported by to target cells where a response is initiated
o neurotransmitter: a chemical messenger that travels between a neuron and a neighboring neuron to initiate a response, or also a receptor on a target tissue
• the response that is triggered is similar to that of an allosteric control, interaction by non covalent bonding w/o chemical changes in either the messenger or the receptor site
• hormones are the chemical messengers of the endocrine system
o produced by specialized cells. tissues, organs
o blood stream vehicle to carry
o effects produced are generally slow and long lasting
o one hormone can affect many different tissues in a variety of locations
o neurotransmitters are the chemical messengers of the nervous system
electrical signal are carried along nerve fibers
in general there is Not direct contact with their targets
neurotransmitters are carried along a gap which separates the neurons or the target organs
released in short burst, degraded rapidly consequently effect is short lived
Section 20.2
• see figure 20.1 page 576
• endocrine system: a system of specialized cells, tissues, and ductless glands that excretes hormones and share with the NS the responsibility for maintaining homeostasis in response to “insult”
• all hormones are excreted into the blood stream
• sometimes endocrine function is shared with organs, which have non-endocrine function. The pancreas secrets insulin and glucagon into the small intestine via ducts
• the key is that hormones themselves do not carry chemical pathway Rxs but only regulate them
• the master gland is the hypothalamus which is a tiny organ at the base of the brain
• the hypothalamus communicates w/ the rest of the body by three mechanisms
direct neutral control: the adrenal gland which sits on top of the kidney is under direct neural control by the hypothalamus
direct release of hormones: hormones produced by the hypothalamus are stored in the posterior pituitary where they await a signal to be released
indirect through the release of regulatory hormones: the most common of regulatory pathways, hormones from the hypothalamus stimulate or inhibit the release of hormones made by the anterior pituitary
• classification:
o polypeptides
o steroids
o amino acid derivatives
• see table 20.1 page 577
• see figure 20.3 on message delivery. Two types:
o the signal must enter the cell and act on a cytoplasm receptor, which then acts on the DNA as repressor or activator. These are hydrophobic in nature and cross the cell membrane easily
o polar, polypeptide and polar, amine hormones cannot cross the cell membrane and consequently, they exert their response through a secondary messenger, which then sets off a cascade of events.
Section 20.3 Epinephrine: Flight or Fight
• see figure 20.3 page 578
• epinephrine is also known as adrenaline
• the function of epinephrine is to increase the permeability of a cell membrane so that more glucose can enter a cell under stressful conditions
• since epinephrine cannot enter a cell membrane because it is hydrophobic in nature, note the large bulky aromatic ring. This molecule has both an alcohol and amine component. The proper name for this compds:
o 4-[1-Hydroxy-2-(methylamine)ethyl]-1,2-benzediol
o found in the L form
o L form of the amino acid is active
• information transfer is predicated on three membrane bound proteins:
o the receptor itself: a transmembrane protein
o G protein found on the cytoplasm side
binds GTP GDP
o enzyme called adenylate cyclase which catalyzes the conversion of ATP cyclic AMP
this in turns activates a kinase which trips glycolysis
• see sequence events page 579
• functions:
o increase the glucose movement into a cell
o increases heart rate
o increases blood pressure
o increases respiratory rate
o decreases blood flow to GI tract. Why?
Section 20.4 Polypeptide Hormones
• represent the largest class of hormones
• TRH is Thyroid release hormone
o modified tripeptide
o released by the hypothalamus
• TSH is Thyroid stimulating hormone
o 20 amino acids in size in two chains
o TRH stimulates release of TSH
o this triggers release of Thyroxin
• Vasopressin:
o posterior pituitary
o blood pressure regulation
o antidiuretic hormone
• Oxytocin:
o posterior pituitary
o responsible for smooth muscle contraction of the uterus
o causes release of breast milk
• Insulin:
o produced by cells of the islet of Langerhans in what is called the β cells
o reduces blood glucose levels by promoting the formation of glycogen from glucose, enhances formation of fats and proteins, however, brain tissue is NOT dependent upon insulin for proper function, they are dependent upon a process of facilitated diffusion, only on glucose concentration dependence
Section 20.5 Steroid Hormones
• see page 582 for the general structure of a steroid
• note the large hydrophobic character
• note the four fused rings
o three are cyclohexane
o one is a cyclopentane
• three functional types:
o mineralococorticoids
adrenal cortex
• aldosterone
o regulates fluid balance of Na and K ions
o glucocorticoids
adrenal cortex
• hydrocortisone
• regulates glucose metabolism
• inhibits inflammatory response
o sex hormones:
testosterone and androsterone
estrone and estradiol which are both made from testosterone
progestin:
• progesterone
o second half of the menstrual cycle to prepare the uterus for implantation of fertilization of the ovum is successful
Section 20.6 Amino Acid Derivatives as Hormone
• because of the blood brain barrier, the chemical messengers which are made endocrine system can not affect the brain
• epinephrine is also made by the NS from the amino acid tyrosine
o therefore it both a neurotransmitter and a hormone
o dopamine is also another neurotransmitter
o norepinephrine is also another which is both a neurotransmitter and a hormone
• Thyroxin is hormone that contains Iodine
o also called T4
o it is a non polar hormone and acts w/o a secondary messenger
o influence metabolism
Section 20.7 Neurotransmitters
• neurotransmitters are the chemical messengers of the NS
• released from neurons and transmit signals to targets:
o cells
o tissues
muscle
endocrine cells
• process depends on the following structural sets:
o see figure 20.6 page 584
dendrites
• receives the neurotransmitter signals
axon
• synaptic vesicle
o hold neurotransmitter
cell body:
• supports the activities of the neuron
o synaptic cleft:
region over which the neurotransmitter travels
• nerve impulses are transmitted along axons and dendrites by changes in electrical potential maintained by active transport mechanics (t be discussed later)
• neurotransmitter molecules must be released from the pre-synaptic vesicles from the axons into the synaptic cleft
o these molecules are synthesized here
o stores in vesicles
o released only when a message is presented
• these neurotransmitters migrate across the synaptic cleft until they reach their target sites on a dendrite or some other target w/ a receptor
• once the target is reached, allosteric like associations hold the transmitter molecule to the receptor of the target
• only they after this non-covalent association has occurred will a message be delivered
• the message is delivered to a dendrite and then this neuron transmits this message along its own axon to the next target as required
• once message is delivered, usually with 15 milliseconds the neurotransmitter must be removed by an enzyme (destroyed) or just taken up and placed in storage in vesicles again
• tyrosine based
o dopamine
o norepinephrine
o epinephrine
• tryptophan based:
o serotonin
o melatonin
Section 20.6 and 20.7 Agonists and Antagonists
• see page 586 list for bullet point procedure
• the key here is that the neurotransmitter must be destroyed or recovered, it cannot remains attached to the target or the target will continue to fire until it is fatigued
• synapse: the place where the tip of a neuron and its target lie adjacent to each other
• drug: any substance that alters the body function when it is introduced from an exogenous source
• agonist: a substance that interacts with a receptor’s normal biochemical response to enhance the affect
• antagonist: a substance that blocks or inhibits the normal biochemical response of a receptor
o competitive
o non-competitive
o irreversible
• acetylcholine:
o nicotine stimulant low doses
stimulant for release of dopamine
o nicotine inhibits high does
blocks acetylcholine receptors and cause them to degrade
• tubocurarine:
o competitive antagonist for acetylcholine
o relaxes the muscles
o blocks the action of respiratory muscle
20.8 Histamine and Antihistamine
• Histamine is the neurotransmitter responsible for the symptoms of allergic response
• produced from the AA histidine
• anti-histamines counter the inflammatory response of histamine
o competitive inhibitor histamine
• histamine activates the production of stomach acid
20.09 Serotonin, Norepinephrine, Dopamine, Health
• monoamines:
o serotonin
o norepinephrine
o dopamine
• all are linked to mood development
• drug addiction
• pleasure
• pain
• mental health
• depression is the result of deficiency of monoamines
• if tricyclic antidepressants prevent reuptake of monoamines and hence elevate mood
• MAO will allow monoamine concentrations to rise at the level of the synapse
20.9 and 20.10 Dopamine and Drug Addiction
• dopamine plays a role in emotion and behavior through interactions with five different kinds of receptors in different parts of the brain
• over supply causes schizophrenia
• undersupply cause fine motor loss
• tied to brain pleasure system
• cocaine blocks the uptake of dopamine from the synapse
o page 434
• amphetamines accelerate the release of dopamines
• increased dopamine levels to alcohol and nicotine addiction
• if the brain cells adapt to the presence of these chemicals, more stimulation may be needed
• marijuana also causes an increase in dopamine levels in the same brain area where heroin and cocaine demonstrate a need for increased dopamine levels following administration of heroin and cocaine
20.12 Neuropeptides and Pain Relief
• key ==> morphine and opium derivatives act on specific receptors of the brain
• here are plant chemicals acting on receptors which were acting on animals receptors
• the question then comes to be is there animal receptors acting in the same manner?
• see chemical structure page 434
• similar structures which are all addictive
20.11 Drug Discovery and Design
• plants were obviously the first source of drugs
• need to start w/ the structure of the plant chemical and improve upon it
• this is called designer drugs
• see page 593
• reaction sequence
DNA
• when a cell is not actively dividing, its nucleus is occupied by chromatin which is a tangle of fibers composed of proteins called histones and DNA
• during cell division, the chromatin organizes itself into chromosomes
• each chromosome is made up of genes, of which in a human there is 100,000 genes but only 10,000 might be important. There is an estimate of about 1 to 3 billion
nucleotides among 23 pairs of chromosomes.
• Current number may be as low as 15,000 - 20,000 and other estimates put the number at 30,000. 50 % of your DNA is found in an apple. We all differ by as little as .1%.
Composition of Nucleic Acids
key definitions:
• nucleic acid: polymer of nucleotides
o DNA
o RNA
• nucleotide: a molecule consisting of a five carbon sugar bonded to a cyclic amine base and one, two, or three phosphate groups; a monomer for nucleic acids
• sugars:
o see page 742 for difference in sugars in position 2
o ribose
o deoxyribose
• bases: 741
o purines
adenine (both DNA and RNA)
guanine (both DNA and RNA)
o pyrimidines
cytosine (both DNA and RNA)
thymine (DNA only)
uracil ( RNA only)
• sugar + base == nucleoside: a molecule consisting of a five carbon sugar bonded to a cyclic amine base, like a nucleotide, but missing the phosphate group
• nucleoside + phosphate == nucleotide
o nucleotides building blocks of all nucleic acids are the monophosphate esters of nucleosides
• typically named using the 5’ designation for the location of the phosphate group
o adenosine 5’ monophosphate page 745
o this is an ribose based sugar
• ribonucleotide; a nucleotide containing the sugar D-ribose
• deoxyribonucleotide: a nucleotide containing the 2-deoxy-D-ribose sugar
• see table 26.2 page 743 + bullets on 744
Structure of Nucleic Acid Chains
• both types are polymers of nucleotides
• connected together by the 3’ OH group and the phosphate group on the 5’ carbon
• called phosphate ester linkages ( phospho-ester bonds)
• no matter how long the polymer is, the free phosphate is always on the 5’ carbon and the OH group on the free 3’ carbon page 746
• the sequence is described as starting at the 5’ end and identifying the order of occurrence of each base
• use letter of A, T, G, C, and U for short hand
• the 5’ information strand corresponds to the N-terminal of the protein chain page 746
Primary Sequence
• the structure can be divided into two parts:
o the backbone of the molecule
o the bases that are the side chain groups
• each phosphate group is linked to a 3’ carbon deoxyribose unit and simultaneously linked to the 5’ carbon of the next deoxyribose unit
• similarly, each sugar unit is linked to one phosphate group at the 3’ position and to another 5’ position
• thus the backbone of DNA (also RNA) is that the chain has two ends, 3’ –OH (one the sugar) and a 5’ OH group which is linked to a phosphate group
• this provides the structural stability of the DNA (RNA) molecule
• the bases that are linked to the backbone are called the side chains and provide all the information necessary for protein synthesis
• they used the previous studies of Erwin Chargaff who proved that the concentrations of A and T were the same and G and C were the same
• the order of the sequence of the deoxyribonucleotides provides the primary sequence
• we always write the sequence order from 5’ to 3’ direction
Watson-Crick paring
• 1953
• really a determination of secondary structure of DNA
• work based on the following investigators:
o E Chargaff Rule
o Roslain Franklin X ray diffraction studies
o MauriceWilkins X-ray diffraction studies
• using this information concluded the structure of DNA as a double helix entwined around each other
o double helix: two strands coiled around each other in a screw-like fashion page 747
• concluded that the strand ran opposite each other in an anti-parallel fashion
• the sugar phosphate backbone is on the outside of the molecule
• base paring: the pairing of bases connected by hydrogen bonding
o see figure 26.3 page 748
o for one A there is one T
o for one G there is one C
• thus a purine must always pair with a pyrimidine because the bases of DNA can not stack properly with a purine-purine pair or a pyrimidine-pyrimidine pair relationship
• the based are so paired that they are held together by hydrogen bonds
o for A to T there are two hydrogen bonds
o for G to C there are three hydrogen bonds
• this is called complementary base pairing
• the strength and the shape of the helix is dependent upon the fit and the hydrogen bonding of the bases
• the bases are the key to understanding how DNA functions
Nucleic Acids and Heredity
• cell growth is a continuing on going process
• the process is controlled by the cell clock
• cells spend very little time actually duplicating DNA but spend a lot of time preparing for the duplicating DNA and a lot of time preparing for the actual division of the cell following the replication of the DNA
• each strand is a blue print for then other strand
• two central questions exist
o how does the DNA carry the information?
o How is that stored information interpreted and put into action
• our genetic information is encoded in the sequence of bases along the DNA strand, each time a cell divides, the information is passed on
• information put into action by a series of proteins
• Central Dogma of Molecular Genetics:
o DNA stores genetic information
o RNA reads, decodes, and uses that information to make proteins
o single gene for a single protein
o must use the right gene, at the right time to assembly ourselves
• Three fundamental processes are defined:
o replication: the process by which the copies of DNA are made when a cell divides
this means that each daughter cell has the same genetic information when the cell divides
o transcription: the process by which the information in DNA is read and used to synthesis RNA
information found in DNA is read or transcribed
the products of transcription are RNAs which carry out the instructions stored in DNA out of the nucleus to the sites of protein synthesis
o translation: the process by which RNA directs protein synthesis
the genetic messages carried by RNA are decoded and used to build proteins
Replication of DNA
• replication: the process by which copies of DNA are made when a cell divides
• the replication of DNA molecules starts w/ the unwinding of the double helix
• this can occur anywhere along the DNA strand
• special molecules called unwinding proteins attach themselves to the DNA strand and cause the separation of the DNA helix
• A, T, G, and C are found nearby
• A always pairs with T
• G always pairs with C
• when the DNA strand is opened up, an enzyme called DNA polymerase moves into the replication fork to begin the process of replicating the DNA strand page 753
• one by one the proper nucleotides are added forming hydrogen bonds w/ their complement
• the polymerase catalyzes the formation of the phosphate ester bond between the arriving 5’ phosphate group with the existing 3’ OH of the existing strand
• since each strand is complementary to its old template strand, two identical copies of DNA are manufactured during the replication process
• the process is described as being semiconserative; because following the process of replication, four strands are present, but only two are new
• the net result is that the strand is copied only in the 5’ to 3’ direction
o this is the leading strand
• meaning that the growth of the strand must begin on the 3’ end of the strand being copied
• since the strands are complementary, only one strand meets this condition and grows toward the replication fork, and this is the leading strand
• thus the replication fork keeps moving
• see figure 26.5 page 720
• the other strand which is in the 3’ to 5’ direction must grow in the opposite direction beginning at the replication fork and therefore in can not grow continuously
o this strand replicated by a discontinuous process is called the lagging strand
• instead a series of segments called Ozaaki fragments are formed as the polymerase moves away from the replication fork
o segments are joined by an enzyme called DNA ligase
• error rate is 1 in 10 billion to 1 in 100 billion nucleotides
Structure and Function of RNA
• RNA is similar to DNA in that both are sugar phosphate polymers and have heterocyclic bases
•
• they differ in composition:
ribose sugar
Uracil replaces thymine
smaller than DNA molecules
does not form a double stranded helix
does not store information
make transfer of information possible by:
• transcription
• translation
• information expressed in the form of proteins
three types of RNA vs. one type of DNA
• mRNA
• tRNA
• rRNA
• messenger RNA: the nucleic acids that carry transcribed information from the DNA out of the nucleus to where the site of protein synthesis;
o information for protein contained in the codon
o codon information in form of triplet
o multiple codons can code form same AA
• transfer RNA: deliver amino acids one by one to the site of the growing polypeptide chain with two distinct sites on this clover leaf molecule:
o L- shaped molecule
o single strand of DNA which folds on itself to create Watson-Crick RNA-RNA pairing
o each tRNA is specific for an individual amino acid
• there is an acceptor end on the 3' end of the tRNA
• the activated amino acid complex of AMP-AA is bonded to the tRNA by ester linkage between the -COOH of the amino acid and the -OH group of the 3' side of the tRNA
• w/ the resulting product of AA-tRNA complex and the release of AMP
• 20 specific enzymes for twenty amino acids for 20 specific tRNAs so the wrong AA does not end up on a tRNA
o anticodon end for attach to mRNAs codons
• complementary to the codon of mRNA
• when the paring takes place, the proper amino acid is delivered to its proper place in the growing protein chain
• anticodon is in the form of a triplet to complementary base pair with the codon of the mRNA
• this creates a RNA-RNA hybrid when the codon and anticodon complementary base pair with each other
• ribosomal RNA: outside the DNA but within the cytoplasm of the cell are the ribosomes. Small organelles where protein synthesis occurs.
o each ribosome is 60 % RNA and 40 % protein
o made up of two units:
• 60s
• 40s
• see table 26.3 page 754
Transcription Process: RNA Synthesis
• first stage in transferring the information carried by DNA into protein synthesis
• demonstrates Watson-Crick base pairing:
DNA-RNA
• initiation signal tell where the process begins
• termination signal tells where the process ends
• process controlled by an enzyme called RNA polymerase, actually called DNA dependent RNA polymerase
• growth occurs in the 5’ to 3’ direction but must use the DNA strand, which is in the 3’ –> 5' direction as the template.
• this mRNA and all other RNAs are modified before they leave the DNA
• in this process a section of the DNA helix unwinds
• one strand of DNA is transcribed informational strand
• ribonucleotides assemble along the unwound segment
• one by one the complementary bases are attaché
o described as being a DNA-RNA hybrid
o see page 755 for DNA-RNA hybrid diagram
o result is the mRNA is always 5’===3’ direction
protein N-terminal is 5’ end
protein C-terminal is 3’ end
• all RNAs are made in the same manner
• the DNA strand which is transcribed is called the informational strand
• the DNA strand on which a mRNA is built is called the template strand
• the genetic code relies on a triplets of consecutive bases called codons which code for individual amino acids to be found in a protein
• following reaching a termination sequence, the newly formed RNA molecule contains a base for every base that was on the information strand from the start to the stop codon
• processing of this mRNA must now occur
• gene segments are frequently discontinuous, in that they are often interrupted by nonsense information, this is called an intron which by be excised
• a process which must be completed before a final mRNA is readied for protein synthesis
Genetic Code
• codon: a sequence of three ribonucleotides in the mRNA that codes for a specific amino acid of a protein
• worked out by Marshal Nirenerg in 1961
• code completely broken in 1967
• demonstrate Crick-Watson pairing:
• RNA-RNA
• A-U
• G-C
• genetic code: the sequence of nucleotides coded in triplets of the mRNA, that determines the sequence of AAs in protein synthesis
• almost universal
• almost same ribonucleotides for same amino acids
• suggests all organisms had a common ancestor
• the codon U-C-C is directing incorporation of the AA leucine in the growing polypeptide chain
• 64 possible three letter combinations:
• 3 code for termination
• 1 codes for initiation
• code is described as being degenerate
• codons always written in the 5'---> 3' direction
• see table 26.4 on page 757
• see page 755 for synthesis format
• 5'---->3' DNA informational strand
• 3'----> 5' DNA template strand
• 5' ----> 3' mRNA
• protein is read: N-terminal ------> C-terminal
• described by three (one) letter code
Translation: tRNA and Protein Synthesis
• synthesis occurs outside the nucleus if you are a eukaryotic cell
• synthesis takes place on the ribosomes
• mRNA connects with the ribosome
• the amino acids are available in the cytosol (amino acid pool)
• amino acids are delivered one by one to the ribosome for incorporation into the protein
The five-step process:
1) activation of the amino acid
2) initiation
3) elongation and translocation
4) termination
Activation
• each amino acid is first activated by reacting with a molecule of ATP producing an activated AA complex:
AA-AMP complex
• then the activated amino acid is attached to its particular tRNA with the aid of an enzyme with the general name amino acid synthetase.
o One specific for each amino acid for that specific tRNA, resulting in the freeing of the AMP and the tRNA-AA complex
1) alanine synthetase
2) methionine synthetase
3) etc…….
Initiation
• three step process:
o a single mRNA molecule attaches itself to a 40S ribosomal unit
• can enter only way because of a special 5’ cap that prevents the 3’ end from entering
o the anti-codon of the tRNA containing methionine binds to the codon on the mRNA which represents the initiation signal accompanied by GTP
• signal is AUG
• special tRNA called initiator tRNA brings in the methionine
o then the 60S ribosomal unit combines w/ the 40 s unit with the expenditure of GTP brought in by the methionine tRNA
• the 60S unit carries two bonding sites:
• P site
• the one on the left which supports the growing polypeptide chains
• when the 60S unit attaches itself to the 40S unit, does so in such a way that the P site is right is right where the methionine tRNA already is
• A site
• the one on the right that is where the incoming tRNA will bring in the next amino acid
• also has a codon for the next amino acid in sequence
Elongation
• at this point the A site is vacant, and each of the 20 tRNA molecules can come in and try to fit in an Crick-Watson RNA-RNA paring relationship
• but only one of the 20 tRNAs carries exactly the right anti-codon that corresponds to the codon on the mRNA
• the binding of this tRNA of amino acid 2 to the A site takes place with the aid of proteins called elongation factors
o proteins called elongation factors accompanied with GTP deliver the tRNA containing amino acid 2 to the A site on the ribosome
o GTP is required for proper positioning of the tRNA
GTP is required for each new amino acid positioned on the A site
• once amino acid 2 is at the A site, Methionine is linked to the new AA by a peptide bond by an enzyme called a transferase
in effect. the Methionine is added on top of the second AA which is still attached to its tRNA
• required enzyme: peptidyl transferase
• the empty tRNA from Meth remains temporarily at the P site
• in the next phase; elongation, the whole ribosome moves one codon along the mRNA, exposing a new A site
• with this move, the dipeptide bonded to tRNA on the A site is entirely translocated from the A to the P site by the movement of the ribosome; while the empty tRNA from the old P site dissociates form mRNA and goes back to the pool of tRNAs to pick up another AA
• otherwise, the ribosome will be too crowded, there would be three tRNAs trying to occupy the same ribosome at the same time
Translocation
• then the old A site becomes the new P site, by the shifting of the mRNA along the ribosome 3 ribonucleotide units
o requires an GTP requiring enzyme called a translocase:
result is directed movement powdered by the hydrolysis of a nucleosidetriphosphate (GTP)
GTP required for each translocation event
• after translocation, the newly opened up A site exposes a new codon
o caveat: internal AUG codons are NOT read by the initiator tRNA which brings in methionine
o there are no initiation factors associated with the tRNA which brings in methionine for internal AUG codons
• again the tRNA brings in the appropriate AA to the A site following the shift of the mRNA
• then the peptide on the P site is bonded to the tRNA and its amino acids on the A site
• the entire peptide with its tRNA is translocated to the P site by the movement of the ribosome
• opens up another A site
• process repeats, etc……
Outcomes of Proteins Synthesis
• the net effect is the following for protein synthesis following initiation:
o the next appropriate tRNA binds to the ribosome
o peptide bond formation attaches the newly arrived AA to the growing chain
o translocation takes place to free the second site for the next tRNA
the old A site now becomes the new P site
repeats until termination signals are reached
two GTP are required for the addition of each amino acid
Termination
• after the last translocation, the next codon reads STOP (UAA, UGC, UGA, or UGA)
o tRNA do not bind to these a codons
o cells do not normally contain tRNA w/ these anti-codons
o factors have names like:
RF 1 which recognizes only UAA or UAG
RF 2 which recognizes only UAA or UGA
• RF factors activate the enzyme peptidyl transferase to break the bond between the tRNA and the polypeptide; freeing the polypeptide and the tRNA which is attached to the P site is freed
• then the ribosome dissociates into its two component parts and the mRNA goes its own way, often destroyed after it is no longer needed
• remember: that the protein begins its folding on the ribosome as the primary structure is produced
• remember: many ribosomes can occupy the mRNA at the same time
• remember: the methionine that is started with during initiation is often cleaved if it is not an needed as part of the primary amino acid sequence
• remember: proteins are often modified after they leave the ribosomes in the RER , SRER, and the cytosol
Wednesday, June 09, 2004
amines
Chapter l5
Amines: Compd that has one or more organic groups bonded to a nitrogen atom. (Based on ammonia NH3). These are organic compd, related to ammonia in structure and chemical behavior. The trivalent nitrogen is bonded to hydrocarbon groups (min 1) and hydrogens (max 2).
The classification of the amine is determined by the degree of substitution on the nitrogen atom, not on the nature of the hydrocarbon attached. Unlike alcohols whose classification is dependent upon the nature of the hydrocarbon group arrangement, since only one hydrogen can be attached to the oxygen in an alcohol.
primary secondary tertiary
R = alkyl
R1-N-H
┇
H R1-N-R2
┇
H R1-N-R2
┇
R3 R = aryl
R any other functional
group
"R" groups attached may or slay not be identical.
Nomenclature
1. primary amine: Named by one word substitutive names formed by determining the parent name to which the -NH2 is attached. The final "e" of the name is replaced by the name of the parent hydrocarbon by the systematic ending amine. Recommended for complex amines.
CH3-CH2-NH2 ====> ethanamine
CH3-CH2-CH2-NH9 ====> 1-propanamine
CH3-CH-CH3 ====> 2-propanamine
┇
NH2
Alternatively, the alkyl name of the hydrocarbon group is used, and the suffix amine is affixed. Recommended for simple amines.
CH3-CH2-CH2-NH2 ====> n-propylamine
CH3-CH-CH3 ====> isopropylamine
┇
NH2
CH3-NH2 ====> methylamine
CH3-CH2-CH2-CH2-CH2-NH ====> n pentylamine
Symmetrical secondary and teritary amines with identical groups attached to the nitrogen with the inclusion of the appropriate multipling prefix (di, tri).
Unsymmetrical secondary and tertiary amines (all hydrocarbons not identical) are named as N-substituted derivatives of the primay amine. The primary amine is defined as the hydrocarbon group chosen as the parent amine for the name, and the other groups are treated as substitutents with the locant N.
CH3-CH2 NH-CH3 ====> N methyl, ethanamine
CH3-CH2-NH-CH2-CH2-CH3 ====> N methyl, propanamine
CH3-N-CH2-CH3 ====> N, N-dimethyl, ethanamine
┇
CH3
The amino group is a functional group. group is easily distinguished by the -NH2.
All proteins have a -NH2 group.
The amide has a -NH2 group.
The name amino is used when there is mixed functionality within a compd, based on order of preference. Remember the amino group need not occur at the end of the compd. Therefore, any functional group which occurs on the terminal end of the carbon has preference in assigning
locant.
4 3 2 1
CH3-CH-CH2-C=O ===> 3-amino, butanoic acid
┆ ┆
NH2 OH ===> beta amino, butanoic acid
General Properties of Amines
1. Primary and secondary amines can form hydrogen bonds with themselves ===> a dimer, trimer, etc. This arrangement is similar to that of water. This will elevate the m.p. and b.p. over alkanes of similar MW. However, due to the small electronegativity difference between the N-H bond, m.p. and b.p. are smaller than the MW of corresponding alcohols.
A tertiary amine can not form amine to amine hydrogen bonds. No frees hydrogen! Hydrogens found on the carbons are not "free" to from hydrogen bonds because they are more "tightly held" because the electronegativity difference between carbon and hydrogen is small, a non-polar covalent bond.
Properties
1. Amines of low MW tend to be gases.
2. Generally have a unpleasant odor.
3. 1°, 2°, 3°, and solubility in water is due to the ability to form hydrogen bonds. The greater the ability to form hydrogen bonds with water, the greater the solubility. Solubility is also dependent upon the length of the carbon chains involved in the compd. Unbranched amines up to four carbons in length.
Name solubility g/100 ml water
methylamine v. sol
ethylamine infinitely
n-proplyamine infinitely
n-butylamine v. sol
t-butylamine infinitely (branched)
n-pentylamine ?
n-hexylamine ?
4. Many are absorbed through skin and toxic.
5. Some may be cancer causing agents.
6. Behave as bases when added to water. These compds are Bronsted-Lowery base; hydrogen acceptors. If a hydrogen is accepted from soln, this leaves the -OH group behind. Increase in [-OH] increases the pH.
Ammonium Salts
1. Like any salt, an amine salt is composed of a cation and an anion and is usally named by combing the cation and anion name.
CH3-NH3 ====> methane-mine
CH3-NH3+Cl ====> methylammonium chloride
alt ----------> methanamonium chloride
The name ammonium is used because the compd is considered to be a deriverative of ammonia.
CH3-CH2-NH-CH2-CH3 ====> (CH3-CH2-NH2-CH2-CH3+) Cl-
diethylamine ====================> diethylammonium chloride
N-methyl, ethanamine ==> N-methyl, ethanammonium chloride
Heterocyclic compds
Heterocyclic compds: A ring structure that stay contain nitrogen, sulfur. oxygen in addition ,to carbon: Aromatic structures may be included
ether thiol polyalcohol
1.4 dioxa 1, 4 dithio alpha d-ribose
cyclohexane cyclohexane furanose
Most important ones are found in DNA or RNA
┆
pyrimidine ┆--------> DNA/RNA bases
purine ┆
┆
ribose ┆--------> sugars of DNA/RNA
deoxyribose ┆
Common Examples
Biomolecules
1. amino acids ====> proteins
R-CH-C=O
┆ ┆
H2N OH
general formula for amino acid
2. nucleotides
purine ====> DNA/RNA
3. vitamins
5 hydroxy, 6 methyl, 3, 4 pyridinedimethanol
pyridoxine water soluble B vitamin ===> fat metabolism
4. neurotransmitters
dopamine ===> 4 (2 aminoethyl) 1,2 benzenediol
Amines in Plants
1. Alkaloid: naturally occurring nitrogen containing compd isolated from a plant, usually basic, bitter and poisonous.
2. Bitterness and poisonous is an evolutionary protection mechanism for the plant.
3. Coniine is extracted from hemlock ==> Socrates
4. Atropine found in balladonna. Muscle relaxant. Acts on CNS ==> depresses muscle activity
5. Solanine found in tomatoes arid potatoes. Peel green potatoes of skin. Cut off potato: spruts.
5 proplpeperdine Atropine
Coiine
Solanine
Amines in Drugs
Morphine Codeine Heroin
Table 15.3 Neurotransmitters and Drugs That Mimic Their Action (Sympathomimetics)
Tuesday, June 08, 2004
carboxy acids
1. There are three classes of compds which we are going to discuss, a base compd and two derivatives:
a. carboxylic acids
b. esters ┇derivatives
c. amides ┇
2. Carboxylic acids: a compd that has the general formula of RCOOH. These compds are classified as organic acids. These are generally weak acids, capable of Rx with both strong/weak bases. The bond between the oxygen and the hydrogen atom in the carbonyl group is polar ===> allowing for ionization of H+ from – OH group.
3. Remember the stronger the acid, the more easily it gives up its hydrogen to form the hydronium ion. Organic acids are very weak when compared to HCl.
4. When organic acids are found in fat, they are referred to as fat, they are referred to as fatty acids.
5. Solubility in water is dependent on the polar carboxyl group of the CA for the formation of hydrogen bonds between the acid and water molecules.
6. Hydrogen bonding ==> dimer formation, means that CAs have both a higher m.p. and b.p. when compared to alcohols of similar MW.
7. Dimer formation: a biomolecular unit formed by two identical units
8. Formic, acetic, propanoic and butanoic acids are very soluble in water. Higher MW CAs are more soluble than alcohols, aldehydes or ketones of comparable MW.
Common CAs
a. acetic acid > found in vinegar
b. lactic acid > from glycolysis
c. butanoic acid > racid butter
d. capric acid > limburger cheese
Nomenclature
1. Carboxylic acids are named by removing the end letter "e" from the alkane and adding the suffix "oic acid”.
2. The carbons atoms in the carboxylic acid are always numbered beginning with the carboxyl group.
ethane ====> ethanoic acid
An alternative name using the Greek alphabet:
====> alpha methyl, pentanoic acid
Shampoos frequently use the alternate Greek alphabet.
alpha chloro, pentanoic acid
beta chloro, pentanoic acid
An often asked question is would you do if there was an -OH group attached to the CA. Then:
Or following the Greek alphabet ==>
alpha hydroxy, pentanoic acid.
Does the name sound familar from a typical commerical. Everything you wanted to know about the nomenclature of commerical handsoaps and shampoos but did not want to ask.
Preparations of Carboxylic Acids
1. CAs are prepared by the oxidation of primary alcohols or aldeydes in the presence of an oxidizing agent [O].
1-buatanol =======> butanoic acid
pentanal =======> pentanoic acid
2. Aromatic acids can be prepared by oxidizing a aldehyde side chain attached to benzene ring.
[O]
benzylaldehyde =======> benzoic acid
Reactions of Carboxylic Acids
There are two primary Rxs which CAs undergo:
a. reaction with a weak/strong base
b. esterification
Reactions with Base
1. Rx with base produces what is called: carboxylic acid salt. Remember that both sodium and potassium salts of a CAs are more soluble in water than the parent CA.
i.e. Benzoic acid vs. sodium benzoate
3.4 g/l vs. 500 g/l
Solubility increases 140 fold
butanoic acid sodium butanoate
Name is formed by adding the name of the cation as the prefix and than removing the "e" and adding "oate" to the alkane name of the acid component. The suffix "acid" is omitted.
This reaction occurs both with strong and weak bases. Formation of the salt increases solubility!
Esterification
1. An important class of compds derived from CAs are the esters. Esters are a group of molecules containing the ester functional group. Typically represented by the following formula: RCOOR. The ester is typically recognized by the ether like linkage
-OR. The family name is produced by dropping the "ic" and the "acid" of the acid components and adding "ate"; alcohol component ===> is named as alkyl.
butanol =====> butyl
butanoic acid =====> butanoate
Typical esters look like this:
2. The process of forming an ester is esterification. Esters are produced by the reaction of an alcohol and a CA in the presence of an acid catalyst. Esterification involves the removal of a molecule of water from the condensation of the CA and a(n) alcohol.
The general name for such a Rx in which a molecule of water is removed from two reactants molecules with the resultant formation of one molecule is called a condensation Rx. This reaction is typical of many biological systems.
The name of such a compd is a composite of the alcohol and CA components. The alcohol component is named as a alkyl ==== butanol ====> butyl
Salicylic Acid Esters
SA is found in the bark of the willow tree. It is a molecule which contains both an -OH and
-COOH functional groups. This product is very irritating. However, modifications have made it "less" irritating.
Condensation with methanol ===> methyl salicylate.
Methyl salicylate is poisionous if taken internally in large quantities. Good for topical applications. Frequently described as cell of wintergreen. Found in Heet and Ben Gay (remember the odor test).
SA condensation with acetic acid (ethanoic acid) on the alcohol component ====> Acetylsalicylic acid or as we affectionately know as aspirin™. When taken, it is not completely ionized in the stomach, but once inside the cell, its is more completely ionized where it does damage. WHY ====>?
Glycerol Esters
1. Glycerol is a trihydroxy alcohol that forms the backbone of natural fats and oils when it is esterified to CAs that have long hydrocarbon chains C > 10.
2. Triglyceride, triacylglyceride or TAG
3. Esters are capable of undergoing two types of Rxs.
a. hydrolysis
b. saponification
4. Hydrolysis is the breakdown of a compd by a reaction with water and a catalyst. The H's and O from the water usually add to the atoms in the broken bond. Rx is usually catalyzed by the presence of a strong acid and the process is reversible.
[H2SO4]
ethyl butanoate <-----------> ethanol + butanoic acid
[H2O]
ethyl benzoate benzoic acid + ethanol
(see page 495)
Amides
1. Amides are represented by the following general formula: They contain the amino functional group: -NH2 and C=O carbonyl group. They are derivatives of CAs: the -0H group being replaced with the -NH2 functional group.
RCONH2 <=== general formula 2. Amides are named by replacing the oic acid name of the corresponding CA with the suffix amide. ethanoic acid ===> ethanamide
3. Since the –NH2 group is on the terminal carbon, the location of the –NH2 group in this configuration is assigned locant #1.
4. Nomenclature:
CH3-CH2-C=O CH3-CH2-C=O
┆ ┆
OH NH2
propanoic acid propanamide
CH3CH2CH2C=O CH3CH2-CH2C=O
┆ ┆
OH NH2
butanoic acid butanamide
5. Amides are the "stuff" amino acids and proteins are made of.
6. Hydrolysis of proteins produces amides. Amino acids (AA) are a type of amides, which are the monomers used for the construction of proteins. Digestion of proteins occurs in the stomach and small intestine by organic catalysts called enzymes: pepsin and trypsin, respectively.
7. Properties
a. strong pungent odors
b. short chains soluble in water
c. have higher m.p. and b.p. over alcohols of corresponding MW
d. forms inter/molecular hydrogen bonds.
8. Important amides:
a. protein metabolism > ammonia > urea > kidneys
b. Tylenol === acetaminophen does not reduce inflammation.
N-(4-hydroxyphenyl) ethanamide
c. LSD, lysergic acid diethylamide affects nerve inpluse transmission. Apparently interfere with serotonin. Note the structural similarity between the two compds.
LSD Scrotonin
N, N diethyl -D- lysergamide 5 hydroxytryptamine
Summary of b.p.s. of compds discussed
Increasing b.p.
alkanes ┆
aldehydes ┆
amines ┆
alcohols ┆
carboxylic acids ┆
amides \ ┆/
Additional Nomenclature
alpha keto pentanoic acid
ethanamide CH3-C-NH2
॥
O
Substitutent Name Nomenclature
aldehyes and ketones
1. The name carbonyl compds covers a large group of different compds. What defines a carbonyl containing compd:
In this simplified diagram, there is an oxygen with a double bond to a carbon. What class of compd depends on the composition of the other two sites.
aldehydes written as RCHO would have a general structural formula of:
ketones written as RCOR" would have a general structural formula of:
carboxylics acid written as RCOOH will have a general structural formula of:
esters written as RCOOR' will have a general structural formula of:
amides written as RCONH2 will have a general structural formula of:
carbonyl conn:
2. Another common feature of this carbonyl carbon is the presence of bond polarity which makes hydrogen bonding possible.
The double bond is polarized due to the electronegativity difference between the two atoms.
This provides the potential for oxygen, hydrogen or both to form hydrogen bonds with a polar solvent (intermolectular). Hydrogen bonding is possible, both the b.p. and m.p. increase for that compd class.
solubility difference
CH3-C-CH3 > > > CH3 CH2 CH3
॥
O
Carbonyl; group allows for hydrogen bonds to form with the solvent water.
Nomenclature: Aldehyde
1. Aldehydes are named systematically by replacing the final "e" of the corresponding alkane with the "al" suffix. When a substitutent of any kind is present, the carbon containing the aldehyde functional group is always assigned. position 1.
alkane name -----> aldehyde name
-----> benzaldehyde
Nomenclature: Ketone
1. Ketones are named systematically by replacing the final "e" of the corresponding alkane with "one". The numbering of the chain begins nearest the carbonyl end.
The above would represent appropriate condensed formuli, only w/o the bonds.
* Identification of carbonyl carbon in this case is inappropriate because there is only one possibility.
It is also possible to make a ketone with a ringed compd.
= O cyclohexonone
= O 2 methylcyclohexanone
CH3 acetophenone
mythyl, phenyl ketone
Properties of Aldehydes and Ketones
1. No hydrogen bonding between aldehyde and aldehyde molecules, no hydrogen bonding between ketone and ketone molecules.
2. Polar molecules because of the carbonyl group.
3. Lower b.p. and m.p. than corresponding alcohols because they do not hydrogen with themselves.
4. Simple aldehydes and ketones are water soluble due to the ability to form hydrogen bonds with water. When C > 5, solubility drops sharply. The longer chained aldehydes and ketones start to behave as alkanes.
5. Volatile aldehydes and ketones are inflammable.
6. Some have distinctive odors.
7. Simple ketones are less toxic than aldehydes.
8. To determine toxicity, one needs to look up the values in a Merk index or other reference book. There you will encounter a value called an LD50. This is defined as the concentration which will kill 50 % of the population which is exposed. Frequently a time frame will be provided. A general standard would be a 24 h time interval. The smaller the value, the more toxic the chemical.
9. Short chained aldehyes and ketones are excellent solvents for both organic and polar compds.
10. The following aldehyde and ketone will be used in an future lab exercise. Please make note of their structure.
cinnamaldehyde
camphor
Common aldehydes and ketones
Formaldehyde:
a. colorless liquid at Rt
b. strong suffocating odor
c. can cause bronchial pneumonia
d. contact dermatitis
e. biological systems convert methanol --> formaldehyde
f. disinfectant, preservative
g. may be a carcinoger
Acetaldehyde:
a. sweet smelling, inflammable liquid
b. product of carbohydrate metabism.
c. Structure:
Acetone:
a. general purpose solvent
b. inflammable
c. a solvent which dissolves both in polar and non polar compds.
d. acetone smell can be detected on the breath of a diabetic during severe insulin shock or the death of a diabetic.
Oxidation of Aldehydes
1. Oxidation: in organic chemistry, the removal of hydrogen from a molecule or the addition of oxygen to a molecule.
a.
b.
c.
2. Oxidation with mild oxidizing agents will not affect other function groups. K2Cr2O7/H2SO4 is not considered to be a mild oxidizing agent.
3. An aldehyde group test: Tollen's.
The test uses Tollen's reagent: a reagent (AgNO3 in aqueous NH3) that converts an aldehyde to a carboxylic acid and deposits a mirror like surface on the inside of a Rx flask. Test works well with scrupulously clean glassware! In soln. remain the ammonium salt of the carboxylic acid.
4. Another mild oxidizing agent, used as a test for the presence of aldehydes is known as Benedict's reagent. This test relies on the reduction of copper metal to produce a visible red brick ppt. It is the copper which is being reduced. Benedict's reagent has Cu2+ in a basic soln that converts an aldehyde to a carboxylic acid and yields a brick red ppt of Cu(II) oxide.
Benedict's reagent is frequently used to identify the presence of aldehyde groups in sugars. It is a test for a reducing sugar.
Reduction of Aldehydes and Keytones
1. Reduction in organic chemistry is the addition of hydrogen to a carbon-oxygen double bond (C=O) or to a carbon carbon double or triple bond.
2. This process is the conversion of a carbonyl compd back into an alcohol by adding hydrogen to the C=O double bond. Reduction in organic chem. usually refers to the addition of hydrogen to a molecule:
3. Aldehydes are converted to primary alcohols:
4. Ketones are converted back into secondary alcohols by the same procedure.
5. There are many biological reactions that occur, but they do not use NaBH4. We will study the enzyme, called reducatases later.
6. For those who have the book, the section on hemiacetals and acetals will be saved for our discussion of the carbohydrates.
7. Aldol condensation is NOT germane to this course.
Monday, June 07, 2004
compds of oxygen
Compds of Oxygen
Chapter 14
1. Alcohols: a compd. that contains an OH functional group covalently bonded to an alkane like carbon. General form; R-OH (all types)
2. Hydroxyl group: the name for the -OH group in an organic molecule.
3. phenol: a compd. that has an -OH functional group bonded to an aromatic benzene ring.
-OH
4. Ether: a compd. that has an oxygen atom bonded to two carbon atoms: General form: R1-O-R2
5. Alcohols: have an OH group covalently bonded to a saturated alkane like carbon.
6. Phenols have the -OH group is bonded directly to the aromatic ring. This would be a secondary alcohol.
7. Ethers have an oxygen bonded to two organic groups.
CH3 0 CH3
Key principle: alcohols, phenols and ethers can all be considered as a variation of the molecule of water. Hydrogens are just replaced by organic molecules.
water H-O-H
alcohol R1-OH
phenol Ar-OH
ether R1-O-R2
8. The b.p. of similar weight alcohols vs. ethers vs. alkanes will follow this pattern.
R-OH (all types) > R1-O-R2 > RH (alkane)
Common Alcohols
trival names structures
methyl alcohol CH3OH
n-propyl alcohol CH3CH2CH2OH
isopropyl alcohol (CH3)2CH)OH
ethylene glycol HOCH2CH2OH
glycerin HOCH2CH(OH)CH20H
1, 2, 3 propanetriol
1, 2 propanediol
Nomenclature
1. There are three types of alcohols:
primary alcohol: an alcohol in which the -OH bearing carbon is bonded to another carbon with two hydrogens.
secondary alcohol: an alcohol in which the -OH bearing carbon is bonded to two carbons and one hydrogen. General form: R2CHOH.
tertiary alcohol: an alcohol in which the -OH group bearing carbon is bonded to three other carbons and no hydrogens: General form: R3COH.
confusing ? => (CH3)3COH
Nomenclature
1. Find the longest chain containing the -OH group. This takes preference over single, double and triple bonds as well as any branch points or substitutents.
2. Change the alkane ending. e ---> ol. The ol ending signifies alcohol of -OH group is present.
3. The hydroxyl group must be clearly located. This is described as a substitutive name. Always assign the LOWEST possible locant to the OH group. The common IUPAC substitutive names for a few common alcohols.
CH3-CH2-CH2-CH2-CH2-OH --> 1-pentanol
What kind of alcohol is this ====>
What kind of alcohol is this ====>
These three compds: are called -->
4. Even in the ring system of an cycloalkane, the systematic name for:
-OH cyclohexanol
The presence of only the hydroxyl group it inaccurate to describe 1-cyclohexanol.
5. Substitutents are named and number as in other IUPAC names. Remember that the
-OH group is assigned the lowest possible locant.
6. The presence of the functional group of -OH takes locant priority over the branch.
7. Given a cyclic alcohol, the location of the -OH group is assigned locant #1. Therefore, the count is either in the clockwise or counter clockwise direction. It is inappropriate to assign the number 1 to the name under these circumstances. The -OH group takes priority even over double or triple bonds in a cyclic compd. (beyond scope of this course).
-OH 3-bromocyclohexanol
/
Br
not ====> 5-bromocyclohexanol
General Properties of Alcohols
1. Alcohols have a property of hydrogen bonding. This property is a consequence of the
-OH group. Hydrogen bonding occurs between the -OH group of the alcohol and the water molecule.
2. Straight chained b.p. of C1 --> C12 are greater than the corresponding alkanes.
3. Solubility depends on chain length. Solubility decreases with increasing chain length. Short chained C < 3 tend to infinite solubility because of hydrogen bonding between the alcohol functional group and water. After 5 carbons on length, solubility drops sharply, but branching will tend to increase solubility when comparing alcohols of equal carbon number This is due to the increasing length of the non-polar component of the chain.
CH3-CH2-CH2-CH2-CH2-CH2—CH2-OH
non polar polar
Remember: Like dissolves like. Long chained w/o branching alcohol's the solubility is similar to an alkane!
Properties of Alcohols
1. Alcohols can form hydrogen bonds with themselves and therefore have higher a higher b.p. than corresponding alkanes.
2. Common alcohols are liquids.
3. Lower alcohols (c ≤ 3) infinitely soluble in water.
CH3-CH2-CH2-OH 1-propanol infinite
CH3-CH(OH-)CH2-OH 1, 2-propanediol
HO-CH2-CH(OH)-CH2-OH 1, 2, 3-propanetriol ___________
CH3-CH2-CH2-CH2-OH 1-butanol 7.9 gm/100 ml
HO-CH2-CH2-CH2-CH2-OH 1, 4-butanediol infinite
(CH3)3COH 2-methyl, 2-propanol infinite
* branching increase solubility with same carbon i.e. 4 which as a normal alcohol was low. Branching "rounds up" molecule, less surface area, therefore increasing solubility.
CH3-CH2-CH2-CH2-CH2-OH 2.3 gm/100 ml
1-pentanol
2-methyl, 2-butanol
4. Alcohols are considered to be weak proton donors hence capable of hydrogen bonding. Alcoholic solutions are neutral and non conductive.
5. Common alcohols are flammable and toxic.
6. Dehydration and oxidation are common reactions.
Dehydration: a more complicated example.
The previous examples are easy to understand, because there is only one possible product. However, it is possible for multiple products to form depending on the location of the -OH group and the presence/absence of branches.
H+
┇-------- > CH3-CH=C-CH3 + H2O
┇ ┇ major product
┇ CH3
┇ 2-methyl-2-butene
┇
┇ H+
┇-------- > CH3-CH2-C=CH2 + H2O
┇ minor product
Name ====> CH3
NAME ====> ?
The double bonds tend to form between 3 and 2 carbons before 3 and 1. Double bonds tend to from between two 2 carbons before between 2 and 1 carbons.
H+
┇-------- > CH3-CH=CH-CH3 + H2O
┇
┇ 2-butene major product
┇
┇
┇ H+
┇-------- > CH3-CH2-HC=CH2 + H2O
Name→
1-butene minor product
In this example, a bond tend to form between 2 and 2 not 2 and 1.
In each set, the two compds formed are isomers.
It is also possible for the same dehydration to occur in cyclic alcohols
-OH +H2O
cyclohexanol --> cyclohexene
Reactions of alcohols: Oxidation
1. Oxidation: In organic chemistry, the removal hydrogen from a molecule or the addition of oxygen to a molecule.
2. Primary and secondary alcohols are converted into carbonyl containing compds on treatment with an oxidizing agent.
3. Carbonyl group: a functional group that has a carbon atom joined to an oxygen atoms by a double bond.
4. Many different oxidizing agents can be used:
a. HNO3
b. KMNO4
c. Na2Cr2O7
d. K2Cr2O7 (in lab)
5. The effect of an oxidizing agent is the removal of two hydrogens. One originates from the -OH group and the other hydrogen comes from the carbon atom bonded to the -OH group.
<---- ┆
----> -C= + H2O
<----
6. The products produced from these oxidation Rxs depend on the structure of the starting alcohol and the Rx conditions.
7. Primary alcohols, those alcohols with the -OH group on a primary carbon can be converted into two products depending upon reaction conditions.
[O] = oxidizing agent
[O] [O]
--> -->
1 alcohol --> aldehyde --> carboxylic acid
More Examples of Oxidation
[O]
┇-------- > CH3-CH2-CH2-C=O + H2O
┇ ┇
CH3-CH2-CH2-CH2OH --------┇ H
┇ butanal
┇
┇ [O] [O]
┇-------- > -------- > CH3-CH2-CH2-C=O + H2O
┇
OH
butanoic acid
8. Aldehyde: a compd. with the -C=O functional group. Can be abbreviated by the following formula:
RCH=0
9. Carboxylic acid: a compd. with the -COOH functional group. Can be abbreviated by the following formula:
RCOOH
10. Ketone: a compd. with the carbonyl carbon bonded to two carbons. Abbreviated by R2C=0
11. Secondary alcohols (described as R2CHOH) are converted to ketones by treatment with an oxidizing agent. The Rx proceeds no further.
[O]
┇-------- > CH3-C=O dimethyl, ketone
┇ ┇
┇ CH3
┇
┇
┇ [O] [O]
┇-------- > CH3-C=O ----> no Rx
┇
CH3
12. Tertiary alcohols do not normally react under these conditions: that is all you need to know.
13. Cyclic alcohols can also follow that same pattern.
-OH =O
cyclohexanol cyclohexanone
Acidity of Alcohols and Phenols
1. Alcohols and phenols are weakly acidic, however, that low acidity is not detectable with the simple pH paper. The ionization pKa's are < < < < < < < small.
2. If we were to rank levels of acidity, the ranking with be as follows:
phenols > alcohols > water
All have pKa's close to water, however they are slightly greater than 10-7.
3. The presence of acidity is predicated on the ionization constant; pKa of the compds.
4. The following equations show the ionization of the three compds compared above. The dissociation is slight. There is an establishment of equilibrium. Unlike HCl, which is completely dissociated in water. Think of ionization constants.
HCl + H2O ------> H3O+ + CI-
H2O + H2O <-----> H3O+ + H+
CH3-OH + H2O <-----> H3O+ + CH3O-
(same is true of the cyclic alcohols)
Ar-OH + H2O <-----> H3O+ + ArO-
This means that the pKa's will increase from 5 water to the phenols, that is becoming larger than 10-7.
Remember; 10-6 > 10-7
0.000001 > 0.0000001
You will be exploiting the difference in the acidity of the -OH groups of the compd classes in the lab. To identify the presence a phenol vs. alcohol. When you added a strong base in an attempt to increase the solubility of 1-pentanol and a phenol, you should find that solubility increased in the phenol.
Here is the reason.
The addition of a strong base to a phenol results in the following Rx:
Ar-OH --------> ArO-Na+
phenoxide
phenoxide is more soluble than the phenol
Ethers
1. Ethers are written with the general formula of:
R1-O-R2
2. Remember that ethers are derivative of water.
R1-O-R2 vs. H-O-H
3. Ethers have the following properties:
a. no hydrogen bonding occurs between the ether molecules, but they are polar. Have a b.p. lower than the corresponding alcohols of similar MW, but have a higher b.p. than the corresponding alkanes.
b. Lower m.w. ethers are volatile and inflammable.
c. Ethers are slightly water soluble to insoluble in water.
d. Forms explosive peroxides on standing, must be stored under inert atm and cold temperatures.
4. Water solubility is due to the ability of the ether oxygen to hydrogen bond with water.
5. Ethers demonstrate alkane like behavior, which is expected with the alkane like component. This means that the alkyl portion is capable of under going substitution Rxs.
Ether Nomenclature
1. There is no systematic ending for the ether linkage. Ethers are named by considering the R-O- as a substitutent that replaces H in the parent compd. Since it is assumed that there is an "O" between the substituted groups, you need no identify the location. Simple nomenclature is to name each of the substituted groups and add the word ether. Use the prefix "di" when indicated!
CH3 O CH3 dimethyl, ether
CH3 O CH2 CH3 ethylmethyl, ether
CH3 CH2 O CH2 CH3 diethyl, ether
==> sometimes you may encounter a name like this if both groups are identical.
ethyl ether ====> diethyl ether
2. Ethers can also be cyclic. A cyclic compd. containing something other than carbons is called: a heterocyclic compd.
3. Typical examples include:
propylene oxide dioxane tetrahydrofuran
(THF)
Dioxane and tetrahydrofuran are typical organic solvents. However, dioxane is classified as a class one carcinogen and should not be encountered in normal circumstances. Dioxane is contaminate of agent orange which was in jungle defoliation in Viet Nam.
4. Common ethers that you will encounter are:
1. diethyl ether ==> early anesthetic
2. some ethers used are derivatives of many common, ethers made by halogenation.
H H H F2/light F F F
H-C-C-O-C-H --------> F-C--C-O-C-F
H H H Cl F F
ethers conn:
5. You will be required to recognize "simple ethers". Name as a substitutive.
6. Remember: Fammability/voltality is reduced, due to the presence of the halogen.
Sulfur containing Compds
1. Sulfur is found in group 6A, it is immediately below oxygen.
2. These presence of sulfur in group 6A dictates that sulfur can replace oxygen in many compds.
3. This means that sulfur containing compds are also derivatives of water.
4. A common name for a sulfur containing compd: mercaptan.
5. The appropriate IUPAC name for a sulfur containing compd.: thiol.
6. Nomenclature of the sulfur containing compds is relatively simple.
a. the systematic parent name of a thiol is formed by adding thiol to the parent name. No letters are removed from the parent name.
CH3-CH2-S-H Ethanethiol
CH3-CH-CH2-CH2-S-H 3-methyl, 1-butanethiol
┇
CH3
CH3-CH=CH-CH2SH 2-butene, 1-thiol
CH3-CH-CH3 2-propanethiol
┇
SH
7. Thiols have a strong appalling odor. Skunk scent and many animal musks fall into this category. May be found in musk perfumes.
8. The "smell" from natural gas is really a mercaptan, methane has no odor.
9. A common reaction can occur between two thiols to form a disulfide compd. This is a very important reaction in the formations of disulfide bridges in protein structure.
Wednesday, June 02, 2004
Chemistry 1020 Notes General Metabolism
Chapter 21
Generation of Biochemical Energy
• All living things must do mechanical work and to accomplish this purpose they all need energy
• this includes the ability to move form one place to another: motion
• this includes the need to move ions and molecules into and out of the cell to maintain homeostasis
• production of energy: includes the process of catabolism
• consumption of energy: includes the process of anabolism: synthetic functions
key: energy is to be released or stored sequentially in the competitive
processes of maintaining internal balance with the organism under times of insult (stress)
key: the energy must be used or stored in the right amounts when
demands or stresses are placed on the biological system
key: how do we maintain homeostasis?
Energy Requirements
• energy must be released from food gradually
• energy must be stored in an easily accessible form
• the release must be finely tuned and delivered exactly to the site where the demand is imposed
• just enough energy must be released to prevent the burning up of the cell during catabolism
• energy must be captured and delivered in some other form other then heat to drive biochemical processes which are not favorable at body temperatures because they are endothermic at 37oC for humans
Free Energy and Biochemical Reactions
key definitions: page 601
• reactions, which are spontaneous, that is favorable in the forward reaction release energy and that energy can then perform work.
• exergonic: reactions, which are the source of biochemical energy
• spontaneous
• exergonic and exothermic are not the same things. exergonic is by definition applies to the release of free energy as defined by the value of G is negative. Page 600
• exothermic where - H applies only to the release of heat
• in reactions in which the products are of higher energy than the reactants, typical in the synthesis reactions, free energy needs to be added, this would be an endergonic process. Requirement for biochemical energy
• here the is positive, the more positive the G value is, the more energy would be required to convert reactants to products. More order will be found: i.e. building glycogen molecules in the liver, assembly of a protein form amino acids, etc….. This is the process of reduction.
key: energy stored in our food sources is released in exergonic processes to power our biochemical demands. Food sources are oxidized from reduced states. Bigger molecules smaller ones;
which can be used to make ATP from ADP + Pi
Metabolism and Energy Production
• metabolism: the overall sum of catabolism and anabolism
• catabolism: metabolic reaction pathways that breakdown
food molecules and release biochemical energy to build ATP
• anabolism: metabolic reaction pathways that build larger biochemical molecules from smaller pieces by expending ATP
key: reactions are finely controlled by sequenced enzyme
pathways: enzyme cascades controlled by feedback
control mechanics
key: page 606 at the conclusion of Step 1 and Step 2 of catabolism, there is a common end product, called Acetyl-SCoA; read as acetyl coenzyme A; it is an important intermediate in the breakdown of food molecule and will be a key controlling point for both catabolism and anabolism.
key: some of the carbons which entered glycolysis will leave the
citric acid cycle as carbon dioxide and must be exhaled
key: some energy leaves the citric acid cycle in the form of ATP,
(from GTP) called substrate level phosphorylation.
key: oxidized molecules from the Citric Acid cycle in the form:
NAD+ are reduced to NADH/H+
FAD is reduced to FADH2
key: NADH/H+ and FADH2 molecules contain a lot of energy, this will be used to make ATP and water in the presence of oxygen using two different coupled concurrent pathways
1. oxidative phosphorylation: ATP synthetase to make ATP
2. electron transport: cytochromes move e-
• Four stages: Overall Review
1) Bulk food is digested in the mouth , stomach, and small intestine to yield small molecules. i.e monosaccharides, individual fatty acids and individual amino acids
2) monosacharides, individual fatty acids, amino acids are degraded in the cytoplasm of cells to yield Acetyl-SCoA
3) Acetyl-SCoA is oxidized inside in the mitochondria by the citric acid cycle to yield carbon dioxide and reduced coenzymes (NADH/H+ and FADH2)
For the electron transport,
4) the reduced coenzymes are used to make ATP from ADP with a mitrochondrial ATP synthetase with concurrent production of water from oxygen. This is indeed an aerobic process. continued formation of water keeps the process going. why?
• Pathways that are possible in the metabolic process:
o 1. linear: Glycolysis
o 2. cyclic: a series of reactions
regenerate the starting material
Citric Acid Cycle
o 3. spiral: a series of reactions in
which enzymes progressive building or tearing down of molecules; Fatty acid spiral for tearing down fatty acids
ATP and Energy Transfer Strategies
Adenosine Triphosphate: the principal molecule for transport of
biochemical energy. Energy Currency The removal of a phosphoryl group results in the formation
of an ADP molecule from an ATP molecule. The removal of the phosphate group is the method used for the transfer of energy. Page 607
• the direction of ATP + H2O ADP + HOPO32- is an exergonic process, it is spontaneous, with a G of negative; exergonic hydrolysis
• obviously the reverse is endergonic; meaning this is the way energy is being transfer to storage
• ATP is the perfect storage vehicle because in the absence of a catalysis, the rate of hydrolysis is slow
• implication is that a catalyst is required for significant hydrolysis. This means that the cell will not self-destruct with this high-energy molecule. However, the cell does not store ATP in a tank, like we store gasoline, ATP’s’ energy is stored in assembled molecules of order: proteins, TAGs, glycogen, proteins, lipids
• second, that the exergonic and endergonic process value of
- 7.3 kcal/mole or 7.3 kcal/mol is an intermediate value, just the “right” value for successful metabolism
• if the energy requirement was too high for synthesis of ATP from ADP, then, some biochemical pathways would not be able to provide the necessary energy to make additional ATP; by coupling its phosphorylation with an exergonic reaction in a reaction cascade: making production of ATP possible from ADP
Energy Coupling Mechanism: 610
key: if energy is released at one time, or release slowly from
a meal, the same amount of energy is released, this is based
on our idea of the Law of Conservation of Mass and
Energy.
key: catabolism takes advantage of releasing the energy slowly
in steps
key: enzyme cascades
key: to determine if a series of reactions are exergonic, sum up
all the pathway’s free energy, and if the pathway 1
+ pathway 2 + etc… has a (free energy) change of negative; then the cascade can occur.
key: not all the steps have a free energy change of negative,
the net is what is important
unfavorable Glucose + HOPO32- G6P + H2O G = + 3.3
favorable ATP + H2O ADP + HOPO32- + H G = - 7.3
favorable Glucose + ATP G6P + ADP G = - 4.0
• the phosphorylation of glucose is essential first step in the utilization of glucose for all pathways
• here the stored energy of one compound is transferred to another, the energy in ATP is transferred to glucose molecule in the form of a phosphate making glucose-6-phosphate
• the reverse is true of the endergonic process for the formation of ATP; here the has a value of + 7.3 kcal/mole, an endergonic process, for this process to work, this process needs to be coupled with an Rx that releases more than 7.3 kcal/mole
Oxidized and Reduced Coenzyme
• many metabolic reactions have both an oxidation and a reduction component, this is called redox
• to meet this requirement, coenzymes recycle back and forth between reduced and oxidized states:
• NADH, H+ NAD+
• as an oxidizing agent, these coenzymes accept hydrogen
• as a reducing agent, these coenzymes supply hydrogen
• NAD+ is found in catabolic pathways and must be reduced to provide energy for the synthesis of ATP
• Note this important change: NADPH,H + is found in anabolic pathways the reduced coenzymes use ATP for the production of more complex materials. This is a reducing reaction and hence the need for the reduced coenzyme. It becomes NADP+ only after it has given up the hydrogens to make a more complex molecule.
Key coenzymes
Behaving as
oxidized reduced
will be reduced will be oxidized
Nicotinamide adenine dinucleotide NAD+ NADH/H+
Nicotinamide adenine dinucleotide NADP+ NADPH/H+ builiding complex molecules
phosphate
Flavin adenine dinucleotide FAD FADH2
Flavin mononucleotide FMN FMNH2
oxidation: can be described as a loss of electrons, loss of hydrogens
or the addition of oxygen
reduction: can be described the gain of electrons, gain of hydrogens, or the loss of oxygen
key: there are two electrons , which are carried, are involved in the formation of the bond in the reduced form, page 612.
The “extra hydrogen” is in solution around the coenzyme.
The coenzyme is capable of entering the active site of
an enzyme w/o inhibiting. It enhances the catalytic effect of
the enzyme.
key: because the coenzymes have picked up electrons in the formation of bond in this process, they are often described as electron carriers.
key: when the reduced coenzymes are oxidized, they must pass
on the electrons as well to form bonds with diatomic oxygen
with the result being the production of water. This is
described as being an aerobic process. Without the
presence of oxygen and the concurrent production of water
the process would come to a halt. However, the sulfur
bacteria use sulfur as an terminal electron acceptor, or
hydrogen acceptor and produce H2S.
i.e. Thiobacillus ferroxidans: found associated with coal
pyrite.
The Citric Acid Cycle
see text page 588
Conditions for the continue cycling of the process:
1. constant supply of acetyl groups to form acetyl-SCoA
2. presence of the oxidizing agents of FAD and NAD+
• to meet condition two, the reduced coenzymes must be oxidized by the electron transport system
• this is stage four of metabolism
• this stage relies on oxygen as the terminal electron acceptor
step 1: preparation
step 2: preparation
step 3: first critical step, here the first round of the reduced
coenzyme NADH/H+ is produced which is going to be
sent to the electron transport chain
step 4: second critical step; another NADH/H+ is produced
step 5: substrate level phosphorylation for the production of
ATP. (actually GTP is produced first)
step 6: here the only reduced FAD, FADH2, is produced, this
will also be sent to the electron transport system to
make ATP
step 8: this step also makes the reduced coenzyme NADH/H+.
Critical Summary of the Citric Acid Cycle
• production of four reduced coenzyme molecule to make ATP
each NAHD/H+ produces 3 ATPs
each FADH2 produces 2 ATPs
each direct turn of the cycle produced 11 ATPs + 1 GTP
• conversion of an acetyl group to make two carbon dioxide molecules, each carbon dioxide molecule must be disposed of, typically by exhaling or urea
The Electron Chain
• process first proposed in 1961 by Peter Mitchell
• based on the idea of a vectorially organized inner mitochondria membrane
• based on the idea of a proton gradient of 1.4 units of pH difference
• idea based on idea that the inner membrane must be impermeable to hydrogen ions
• the idea that the energy conserving event is the movement of protons across the inner membrane
• at the conclusion of the citric acid cycle, the carbon atoms of the acetyl groups which have entered have been converted to carbon dioxide and release to be exhaled
• the reduced coenzymes which have been formed are ready to donate their energy to generate additional ATP
• remember that at the end of this process, water is produced
• the key, is that both the hydrogens and the electrons will follow different pathways before they are used to produce water from oxygen
• the Rxs of the ETS are coupled with the process of oxidative phosphorylation
• energy released from the ETS Rxs drives the synthesis of ATP by providing the energy to pump electrons from the matrix to the intermitochondrial space
• the enzymes which are required for this process are found in the inner membrane of the mitochondria
• this is an example of how membrane fluidness at work
• the process is based on 5 fixed enzyme groups and two mobile carries, one called coenzyme Q and cytochrome C
• the process:
1. hydrogens from the reduced coenzymes of NAD and FAD enter the electron transport chain at the levels of the complex I and II respectively, this is why reduced FAD produces only two ATP as opposed to three for reduced NAD+
2. electrons are than passed on to increasingly stronger oxidizing agents, remember, here they are taking on e
electrons and what is an oxidized form
3. at three of the four fixed complexes, hydrogens are
moved from the mitochondria matrix to the
inner-membrane space. The hydrogens originate from the matrix and not from the reduced coenzymes
4. this creates a concentration gradient, a potential
difference, which is used to power the ATP formation
by the membrane bound ATP synthetase
5. w/o concentration gradient, the process would
come to a halt
6. hydrogen ions can only return to the matrix by
passing through the ATP synthetase gate
7. the enzyme for step 6 of the citric acid cycle is part
of complex II of electron transport. This means that
reduced FAD is not free to wonder about the
mitochondria matrix
8. electron carries move electrons between the different
complex, however, the key enzyme complex is IV,
passes electrons to oxygen atoms which combine with
hydrogen atoms to make water
9. the most difficult question is this, if the last segment of
the ETS can only support one electron at a time, and
the formation of water requires 4 electrons, how does
it manages this feat?
The Cell and Structure
• two cell types, prokaryote and eukaryote
• eukaryotic cells are large than bacteria cells and have the nucleus enclosed by a membrane, called the nuclear membrane
• everything that is found between the nuclear membrane and the cell membrane is called the cytoplasm
• the fluid part of the cytoplasm is called the cytosol
• there are organelles found in the cytosol, the mitochondria is responsible for the generation of most of the cell’s ATP.
• the mitochondrion is a doubled walled organelle w/ a fluid like matrix inside, called the mitochondria matrix. This matrix is important because the common energy producing pathways for digested food molecules; the citric acid cycle, electron transport and ATP production begin in this matrix and are completed in by the enzymes of the inner mitochondria matrix.
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