L2-Enzymes & Enzyme Kinetics

Question 1

LO1: Km definitions (2)

Answer 1

Km defined as ratio of rate constants (unit=moles/liter) that can be measured experimentally–>can reflect the strength of interaction between enzymes and their substrates (Kd=dissociation constant; difficult to measure experimentally)

Also defined as the [substrate] required to attain 1/2 Vmax

Question 2

LO1: Interpret a high vs low Km value

Answer 2

The lower the Km, the higher affinity the enzyme has for the substrate and the tighter it must be binding (less substrate needed to attain 1/2 Vmax, which is where enzyme is saturated)

Question 3

LO1: Define Vmax (2)

Answer 3

Maximum velocity of a Michaelis-Menten following reaction

Peak velocity where enzyme is saturated with substrate, so reaction rate plateaus

Question 4

LO3: Describe competitive inhibitors (4)

Answer 4

1. resemble substrate
2. competes with substrate at active site
3. can be overcome by high [substrate]
4. Change Km (increases) but not Vmax

Question 5

LO3: Describe noncompetitive inhibitors (4)

Answer 5

1. don’t resemble substrate
2. binds enzyme but not at active site (allosteric modification)
3. cannot be overcome by high [substrate]
4. Change Vmax (decreases) but not Km

Question 6

LO5: Describe irreversible enzyme inhibitors (4)

Answer 6

1. bind to active site
2. react covalently with a functional group on the enzyme and stop catalytic cycle (cause inactivation of enzyme)
3. Change Vmax (decreases) but not Km
4. Not reversible; new enzyme has to be synthesized (effects can persist even once they’re removed and are not reversible in cells that lack platelets)

Question 7

LO5: Major clinical examples of irreversible enzyme inhibitors

Answer 7

Fluorouracil: inhibits thymidylate synthase (chemo)
Allopurinol: inhibits xanthine oxidase (gout)
Aspirin: inhibits cyclooxygenase (pain/platelet aggregation)