Enzyme Inhibition

Question 1

What is a reversible inhibitor?

Answer 1

An inhibitor that binds to the enzyme non-covalently.

Question 2

What is a competitive inhibitor?

Answer 2

• resembles substrate structure- competes directly with substrate for active site- binds to the active site but is unreactive

Question 3

What parameters are affected by competitive inhibition?

Answer 3

Km - affecting the affinity for substrate.Vmax is not affected by competitive inhibition.

Question 4

What is an uncompetitive inhibitor?

Answer 4

• binds to an allosteric site on the ES complex - can cause distortion of the active site

Question 5

What parameters are affected by uncompetitive inhibition?

Answer 5

Both Vmax and Km.

Question 6

What is a mixed inhibitor?

Answer 6

• bind to an allosteric site - can bind to free enzyme or ES complex - effective inhibition at both low and high substrate concentrations

Question 7

Which parameters are affected by mixed inhibition?

Answer 7

Both Vmax and Km.

Question 8

What is a non-competitive inhibitor?

Answer 8

• binds at an allosteric site - effectiveness depends on inhibitor concentration

Question 9

Which parameters are affected by non-competitive inhibition?

Answer 9

Vmax lowers as inhibitor concentration increases.Km is not affected as EI can still bind substrate.

Question 10

What are the types of reversible inhibition?

Answer 10

Competitive, uncompetitive, mixed and non-competitive.

Question 11

What are the types of irreversible inhibitors?

Answer 11

Group specific covalent modifying agents, affinity labels, suicide substrates and transition state analogues.

Question 12

What are group-specific covalent modifying agents?

Answer 12

Inhibitors that react with specific types of enzyme functional groups, e.g. Ser-OH, Cys-SH and His-imidazole.

Question 13

What is an example of a group-specific covalent modifying agent?

Answer 13

DIPF which reacts with specific Ser-OH in acetylcholinesterase at synapses, poisoning nerves.

Question 14

What is an affinity label?

Answer 14

Have a similar structure to the substrate and react at the active site, covalently inactivating the enzyme.

Question 15

Give an example of an affinity label.

Answer 15

TPCK - has a phenyl group which binds in the active site of chymotrypsin

Question 16

What are suicide substrates?

Answer 16

Have a similar structure to the substrate and the enzyme treats them as a substrate, starting the catalytic reactions with the inhibitor. This leads to the inhibitor reacting covalently with the enzyme, making the enzyme inactive.

Question 17

Give an example of a suicide substrate.

Answer 17

Penicillin- inhibits transpeptidase, preventing bacterial wall synthesis.

Question 18

What is a transition state analogue?

Answer 18

Have a structure similar to the transition, binding more tightly to an enzyme than a substrate.

Question 19

What are transition state analogues useful for?

Answer 19

-understanding catalytic mechanisms and the structure of the transition state which can not be isolated experimentally.-very specific inhibitors of enzymes in pharmaceuticals.-antigens for immunising lab animals to generate antibodies with binding sites complementary to the transition state.

Question 20

Give an example of a transition state analogue.

Answer 20

Saquinavir is used to inhibit HIV protease in HIV treatment.

Question 21

What is an irreversible inhibitor?

Answer 21

An inhibitor that reacts with the enzyme and changes it chemically.

Question 22

How can competitive inhibition be overcome?

Answer 22

The inhibitor is displaced at high concentrations of substrate.

Question 23

How can uncompetitive inhibition be overcome?

Answer 23

Lowering the concentration of the substrate makes the effect of the inhibitor negligible.