Chapter 7: Enzymes as Drug Targets

Question 1

Types of drugs that act on enzymes

Answer 1

• reversible inhibitors
• irreversible inhibitors
• allosteric site inhibitors
• transition state analogs/inhibitors
• suicide substrates

Question 2

Competitive Inhibitors

Answer 2

• competes for binding with the native substrate
• reversible inhibitors
• acts at the enzyme active site

Question 3

Irreversible Inhibitors

Answer 3

• become covalently bound to the active site
• causes permanent loss of activity
• contain and electrophilicci group that often covalently links to an exposed serine or cysteine
• ex: nerve agents, beta-lactam

Question 4

Allosteric site inhibitors

Answer 4

• allosteric site: where a regulatory molecule binds and influences activity
• drug may mimic a naturally occurring allosteric effector

Question 5

Transition-State Analog

Answer 5

• drug is designed based on the natural substrate’s transition state
• ex: renin

Question 6

Suicide substrates

Answer 6

• irreversible
• first, are modified by the enzyme and then covalently attach to the enzyme
• (enzyme must first modify the substrate unlike irreversible inhibitors)
• example: augmentin

Question 7

How does Augmentin work?

Answer 7

• clavulanic acid inactivates/ destroys beta-lactamase (the enzyme in bacteria that degrades penicillin) then amoxicillin is able to work

Question 8

Km (app)

Answer 8

Km apparent: measured Km with an effector such as a drug
= alpha (degree of inhibition) x Km

Question 9

Inhibition Constant Ki

Answer 9

Ki: EI⇌E+I
- E=enzyme , I= inhibitor
- large Ki=weak binding
= [E][I]/[EI]

Question 10

IC50 values

Answer 10

the amount of inhibitor needed to reduce activity level of enzyme by 50%
- is determined by activity measurement while Ki is a measurement of binding
- can equal Ki when the concentration of the inhibitor is much greater than the concentration of the enzyme

Question 11

EC50

Answer 11

the amount of inhibitor needed to alter a cellular effect by 50%