lecture 19

Question 1

in normal situations does the Km change?

Answer 1

no, only the Vmax can be increased by adding more enzyme concentration.

Question 2

What does a low Km mean?

Answer 2

This reflects a high affinity of the enzyme for the substrate

Question 3

What does a high Km mean?

Answer 3

This means that their is a low affinity of the enzyme for the substrate

Question 4

What are the two kinds of reversible inhibition?

Answer 4

competitive and non-competitive

bind non-covalently

Question 5

What is a competitive inhibitor?

Answer 5

is a structural analog of the substrate that competes
with the substrate for the binding to the active site of
the enzyme.

Question 6

Example of a competitive inhibitor?

Answer 6

statin drug that competitively inhibits HMG CoA reductase which is the regulated enzyme of cholesterol synthesis.

Question 7

how does a competitive inhibitor impact the M-M graph?

Answer 7

It increases the Km, but does not impact the Vmax

Question 8

How does a non-competitive inhibitor impact the M-M graph

Answer 8

Does not change the Km but decreases the Vmax

Question 9

How is the lineweaver-burk different from the M-M graph?

Answer 9

1. It is a straight line…. instead of a hyperbolic curve
2. dont need as many data points (less money)
3. Vmax is mathematically obtained, instead of estimated

Question 10

Why are some inhibitors irreversible?

Answer 10

The drug or poison will bind covalently to the enzyme

Question 11

how to reverse irreversible inhibitors

Answer 11

The enzyme must be degraded and a new enzyme must be made

Question 12

What leads to irreversible inhibition?

Answer 12

1. modification of the active site
2. blocking the sulfhydryl-group enzyme
3. interfere with metal cofactor

Question 13

Explain DFP (di-isopropyl flourophosphate)

Answer 13

it is an irreversible inhibitor of acetylcholinesterase

Question 14

What symptoms does DFP poisoning have?

Answer 14

It leads to an accumulation of acetylcholine thus:

1. blurred vision
2. bronchoconstriction
3. seizures
4. respiratory arrest and death

Question 15

How does DFP inhibit acetylcholinesterase?

Answer 15

The poison blocks a specific serine that forms normally a covalent bond with the acetyl group during catalysis.

Question 16

What kind of inhibitor is aspirin?

Answer 16

irreversible inhibitor

Question 17

What does aspirin inhibit?

Answer 17

COX-1 and COX-2

cyclooxygenase enzyme

Question 18

What is aspirin used for?

Answer 18

300-500 mg pain relief

81 mg for reduced blood clotting

Question 19

How is COX involved in blood clotting?

Answer 19

Thromboxane and prostacycin are involved in blood clotting

Throm- more blood clotting

prosta- less blood clotting

Question 20

What does a low dose of aspirin do exactly?

Answer 20

It inhibits the COX genes in both epithelial cells and platelets

platelets cannot synthesize new COX, thus less thromboxane is made

Question 21

What are suicide inhibitor drugs?

Answer 21

the enzyme itself changes the structure of the drug resulting in an irreversible inhibitor

Question 22

What is an example of a suicide inhibitor drug?

Answer 22

Allopurinol

Question 23

What does allopurinol do?

Answer 23

Xanthine oxidase uses the drug allopurinol instead of hypoxanthine as substrate and forms the irreversible inhibitor drug alloxanthine.

Alloxanthine (oxypurinol) binds irreversibly to the active site of xanthine oxidase and reduces the formation of uric acid

Question 24

What does allopurinol treat?

Answer 24

Gout