Enzyme inhibitors

Question 1

How can inhibitors be applied for drug design?

Answer 1

1. ID target enzyme
2. Find a compound that affects the target enzyme
3. Characterize enzyme-inhibitor interactions
4. Optimize the inhibitor to be developed into a drug

Question 2

What are competitive inhibitors?

Answer 2

Inhibitors that mimic the substrate and compete with it for the active site

Question 3

Can you swamp out a competitive inhibitor by adding more substrate?

Answer 3

Yes

Question 4

What is apparent Km?

Answer 4

Uninhibited Km times alpha. Alpha is 1 + [I]/Ki

Question 5

What is Ki?

Answer 5

Constant for inhibitor binding, which is Ki = [E][I]/[EI]

Question 6

Does a competitive inhibitor affect the y-intercept?

Answer 6

No effect

Question 7

Does a competitive inhibitor affect Vmax?

Answer 7

No effect

Question 8

Does a competitive inhibitor affect slope?

Answer 8

Increases

Question 9

Does a competitive inhibitor affect Km?

Answer 9

Increases

Question 10

What are uncompetitive inhibitors?

Answer 10

Inhibitors that bind to allosteric sites in the enzyme-substrate complex, which inactivates it and doesn’t allow the reaction to proceed

Question 11

Can you swamp out an uncompetitive inhibitor?

Answer 11

No

Question 12

Does an uncompetitive inhibitor affect the y-intercept?

Answer 12

Increases

Question 13

Does an uncompetitive inhibitor affect Vmax?

Answer 13

Decreases

Question 14

Does an uncompetitive inhibitor affect slope?

Answer 14

No change

Question 15

Does an uncompetitive inhibitor affect Km?

Answer 15

Decreases proportionally to Vmax

Question 16

What is mixed inhibitor?

Answer 16

Binds to a site that exists either on the free enzyme or the enzyme-substrate complex and inactivates it

Question 17

Can you swamp out a mixed inhibitor?

Answer 17

No

Question 18

What does the Dixon plot look like for a mixed inhibitor?

Answer 18

The lines intersect before the Y-axis

Question 19

Does a mixed inhibitor affect the y-intercept?

Answer 19

Increases

Question 20

Does a mixed inhibitor affect Vmax?

Answer 20

Decreases

Question 21

Does a mixed inhibitor affect the slope?

Answer 21

Increases

Question 22

Does a mixed inhibitor affect Km?

Answer 22

Can either increase or decrease depending on where the lines intersect

Question 23

What special type of inhibitors has the lines of the Dixon plot intersect on the x-axis?

Answer 23

Non-competitive inhibitor

Question 24

What happens to Km for a non-competitive inhibitor?

Answer 24

No change, since alpha and alpha’ are the same

Question 25

What are transition state analogs?

Answer 25

Molecules that mimic the transition state of an enzyme

Question 26

How do transition state analogs work?

Answer 26

They bind really strongly to the enzyme in the active site by mimicking the transition state, but don’t react

Question 27

How is an irreversible inhibitor different from a reversible inhibitor?

Answer 27

They bind covalently to the enzyme and can’t dissociate which results in permanent inactivation, while a reversible inhibitor uses non-covalent interactions

Question 28

How do mechanism-based irreversible inhibitors work?

Answer 28

The enzyme gets inactivated partway through the reaction, so the reaction doesn’t go to completion

Question 29

How does fluorouracil work as an irreversible inhibitor?

Answer 29

It inhibits thymidylate synthase by looking like a thymine, but has a fluorine at the position on thymine that reacts. The enzyme can’t pull off the fluorine so it stops