Week # 10 - Enzymes
Lecutres - 26, 27, 28
Concepts:
Classification of enzymes - "-ase" in name, by name of reaction
Parts list for an enzyme and how it works.
Inhibitors - reversible competitive and noncompetitive, irreversible, allosteric,
feddback
Applications
Ques. 1: Consult a list of classes of enzymes. Which two types have we studied
reactions in the earlier part of the course?
Ques. 2. a. Explain the difference between the cofactor and coenzyme.
b. Describe the relationships of the following parts of a typical enzyme: cofactor,
enzyme, coenzyme, vitamin, protein.
Ques. 3: a. Explain what is meant by the lock and key theory of enzyme action.
Include: active site, substrate, enzyme.
b. Expalin the Induced Fit Model of enzyme action and contrast with the lock and
key model.
Ques. 4. How does an enzyme distinguish between the correct and incorrect
substrate in the active site?
Ques. 5: Write a paragraph giving a complete summary of all parts of an enzyme
and how it works.
Ques. 6: a. List four factors which may effect how well an enzyme works.
b. From the above factors, list two non-specific enzyme inhibitors. Explain how
they inhibit enzyme action.
c. What happens to the active site and the molecular geometry of the enzyme as
it is denatured?
d. Excess of either acid or base causes denaturing of protein. What type of
bonds are disrupted by this action?
e.
Name some other denaturing methods to inhibit or destroy enzyme activity.
f. If an enzyme has been denatured, is it likely that its enzyme activity can be
restored? Is the inhibition reversible or irreversible? Explain.
Ques 7. Briefly define and explain the actions of the following enzyme inhibitors.
Give some examples:
a. reversible competitive inhibitor
b. reversible noncompetitive inhibitor
c. irreversible inhibitor
d. allosteric inhibitor
e. feedback inhibitor
QUES. 8: If the concentration of inhibitor is less than that of the substrate and
the substrate has a higher affinity for the active site, is the enzyme inhibited a lot,
or a little?
Ques. 9. MSG (monosodium glutamate) is used for a meat flavoring agent. Only
the L optical isomer is effective. After drawing the mirror image, explain why the
D isomer apparently is unable to react with taste receptor sites on the tongue.
O
+
Na
NH2
H2
C
C
C
C
H2
OH
C
H
O
O
Ethanol is metabolized in the body by oxidation to acetaldehyde, which is in turn
further oxidized to acetic acid by aldehyde oxidase enzymes. Normally, the
second reaction is rapid so that acetaldehyde does not accumulate in the body.
Ques. 10: CH3CH2OH + (0) 
+ (0) 
A drug, disulfiram (Antabuse) inhibits the aldehyde oxidase which causes the
accumulation of acetaldehyde with subsequent unpleasant side-effects of nausea
and vomiting. This drug is sometimes used to help people overcome the drinking
habit.
H3 C
CH3
H2C
S
N
H2C
C
C
S
CH3
CH2
S
N
CH2
S
H3 C
QUES. 11: Which part of the disulfiram molecule probably interacts with the
active site of aldehyde oxidase.? Hint: Look for something similar to the -C=O
group.
Methanol poisoning occurs because methanol is oxidized to formaldehyde and
formic acid which attack the optic nerve causing blindness. Ethanol is given as
an antidote for methanol poisoning because ethanol competitively inhibits the
oxidation of methanol. Ethanol is oxidized in preference to methanol and
consequently, the oxidation of methanol is slowed down so that the toxic byproducts do not have a chance to accumulate.
QUES. 12: Ethylene glycol, if ingested, can be poisonous. Ethylene glycol is
oxidized by the same enzymes used in the previous examples by ethanol and
methanol. Describe how ethanol can be used as an antidote.
H2
C
HO
C
H2
dehydrogenase
OH
ethylene glycol
aldehyde
HO
oxidase
H2
C
O
C
H
O
OH
2-hydroxyethanal
C
O
C
OH
oxalic acid
Ques. 13. In the digestion of food, what do the following enzymes do? Give the
substance acted upon and the final products in words. (Need to look in the index
or chap 23 and 25)
amylase,
maltase
lactase
sucrase
lipase
pepsinogen
pepsin
trysin
chymotrypsin
Ques. 14. Enzymes are used for diagnostic testing of health conditions: List 5
enzymes and the conditions that are measured if elevated.
Penicillin Mode of Action - Enzyme Inhibition:
http://www.elmhurst.edu/~chm/vchembook/652penicillin.html
All penicillin derivatives produce their bacteriocidal effects by inhibition of bacterial cell wall
synthesis. Specifically, the cross linking of peptides on the mucosaccharide chains is prevented.
If cell walls are improperly made cell walls allow water to flow into the cell causing it to burst.
Resemblances between a segment of penicillin structure and the backbone of a peptide chain
have been used to explain the mechanism of action of beta-lactam antibiotics. The structures of a
beta-lactam antibiotic and a peptide are shown on the left for comparison. Follow the trace of the
red oxygens and blue nitrogen atoms.
The bacterial cell wall synthesis is completed when a cross link between two peptide chains
attached to polysaccharide backbones is formed. The cross linking is catalyzed by the enzyme
transpeptidase. First the terminal alanine from each peptide is hydrolyzed and secondly one
alanine is joined to lysine through an amide bond.
Penicillin binds at the active site of the transpeptidase enzyme that cross-links the peptidoglycan
strands. It does this by mimicking the D-alanyl-D-alanine residues that would normally bind to this
site. Penicillin irreversibly inhibits the enzyme transpeptidase by reacting with a serine residue in
the transpeptidase. This reaction is irreversible and so the growth of the bacterial cell wall is
inhibited.
Since mammal cells do not have the same type of cell walls, penicillin specifically inhibits only
bacterial cell wall synthesis.
Ques. 15: In your own words explain how the penicillin drug works including enzyme inhibition,
cell wall synthesis, peptide chains, beta lactam structure.
Sulfa Drugs - Mechanism for Action:
http://www.elmhurst.edu/~chm/vchembook/653sulfa.html
Normally folic acid is synthesized in two steps in bacteria by the top reaction on the left. If a sulfa
drug is used, the first enzyme is not to specific and can use the sulfonamide in the first reaction.
This reaction produces the product containing pteridine and the sulfa drug. The next and final
step is the reaction PABA + with glutamic acid to make folic acid. If the sulfa drug has been
substituted for the PABA, then the final enzyme is inhibited and no folic acid is produced.
Recent studies indicate that substituents on the N(1) nitrogen may play the role of competing for
a site on the enzyme surface reserved for the glutamate residue in p-aminobenzoic acidglutamate through one of the following two ways:
a) Direct competition in the linking of PABA-glutamate with the pteridine derivative.
b) Indirect interference with the coupling of glutamate to dihydropteroic acid.
The basic structure of sulfonamide cannot be modified if it is to be an effective competitive
"mimic" for p-aminobenzoic acid. Essential structural features are the benzene ring with two
substituents para to each other; an amino group in the fourth position; and the singly substituted
1-sulfonamido group.
Ques. 16: In your own words explain how the sulfa drug works including enzyme inhibition, folic
acid, and antimetabolite.
Ques. 17. Match the name of the vitamin with its letter designation, give use,
and/or deficiency disease.
Vitamin
Letter
___Thiamine
B6
___Ascorbic Acid
D
___Riboflavin
B2
___Pyridoxine
B1
___Cobalamin
A
___Tocopherol
E
___Retinol
C
___Niacin
B3
Use
Deficiency
___Pantothenic Acid
B5
___Cholecalciferol
B12
Ques. 18. Which vitamins should not be taken in large doses since they are
toxic?
Ques. 19. Which vitamins are likely to be lost by cooking in water? Why?