Enzymes as drug targets - 1

Question 1

What is the role of Enzymes ?

Answer 1

Enzymes catalyse reactions by reducing activation energy

Question 2

Name 5 different catalytic mechanisms

Answer 2

1) Acid-base catalysis - Enzyme donates /accepts protons from enzymes
2) Covalent catalysis - Enzyme binds covalently to substrate
3) Metal ion - Ion stabilises charge in the reaction = water ionization = better nucleophile

4) Proximity and orientation of reactants
5) Stabilisation/binding to transition state

Question 3

What is a Prosthetic group ? give examples

Answer 3

An enzyme co-factor with low molecular weight that binds to an enzyme and participates in the reaction

e. g:
1) H donors (NADH2, NADPH2, FADH)
2) Methyl donors (S-adenosyl methionine)
3) acetyl donors/acceptors (Co-enzyme A)

Question 4

Name examples of Metal ions involved in Catalysis ?

Answer 4

Mg2+, Fe2+/3+ , Zn2+

Question 5

What is the Lineweaver-burk plot used to determine ?

Answer 5

Km and Vmax

Question 6

What is Km?

Answer 6

The concentration of substrate needed to produce 50% of the max velocity of an enzyme

Question 7

What is Vmax ?

Answer 7

Max reaction rate/max reaction velocity

Question 8

What is the Michaelis menten equation used to describe ?

Answer 8

The rate at which enzymes function at different substrate concentrations

Question 9

What is an enzyme drug inhibitor ?

Answer 9

Drugs that interfere with the activity of an enzyme

Question 10

Enzyme drug inhibitors can be Reversible or Irreversible. TRUE or FALSE ?

Answer 10

TRUE

Question 11

Describe a competitive inhibitor. What effect does it have on Vmax and Km

Answer 11

Inhibitor that binds to active site therefore prevents substrate from binding to enzyme.

Vmax = unaltered
Km = Increases

Question 12

Describe a Uncompetitive inhibitor. What effect does it have on Vmax and Km

Answer 12

Binds to ES complex via allosteric mechanism as S binding isn’t affected. Therefore affects catalytic function

Vmax and Km = Decrease

Question 13

Describe a mixed inhibitor. What effect does it have on Vmax and Km

Answer 13

Binds to free enzyme AND ES complex. Allosteric mechanism.

Vmax = Decreases
Km = Increases or decreases

Question 14

Describe an Irreversible inhibitor. What effect does it have on Vmax and Km

Answer 14

Binds to enzyme irreversibly and eliminates a fraction of the enzyme

Vmax = Decreases
Km = Unaltered

Question 15

Name 3 types of drugs that act as Competitive Inhibitors ?

Answer 15

Statins (& HMGCR)
ACE Inhibitors
Phosphodiesterase Inhibitors

Question 16

Name a drug that acts as either competitive or Irreversible ?

Answer 16

NSAID’s (& COX)
e.g:
Aspirin (irreversible)
Ibuprofen (competitive)