Professional Documents
Culture Documents
187 - Biochemistry Physiology) Enzyme Inhibition
187 - Biochemistry Physiology) Enzyme Inhibition
187 - Biochemistry Physiology) Enzyme Inhibition
1. ENZYME INHIBITION
Enzyme Inhibition: Reversible and Irreversible Inhibition Medical Editor: Jona Frondoso
Km and Vmax
(i) Km
Figure 1. Reaction model showing an enzyme reversibly
combining with its substrate to form an ES complex that Reflects the affinity of the enzyme for a particular substrate
subsequently yields product, regenerating the free enzyme. Substrate concentration ([S]) at ½ Vmax
Changes when the equilibrium changes
Where (ii) Vmax
o E is the enzyme
o S is the substrate Maximal velocity
o ES is the enzyme-substrate complex Velocity of the reaction when all enzymes are saturated
o P is the product by the substrate
o k1 is the rate constant for the forward reaction of E Changes when the amount of ES complex formation
and S forming ES changes
o k- 1 is the rate constant for the reverse reaction of ES
forming E and S FYI:
o k2 is the rate constant for the forward reaction of ES Km and Affinity
forming E and P
(i) Small Km
Inhibitor ↑ Affinity of the enzyme for a particular substrate
↓ Concentration is needed to achieve ½ Vmax
Any substance that can diminish the velocity of an enzyme-
catalyzed reaction [Harvey & Ferrier, 2011] (ii) Large Km
↓ Affinity of the enzyme for a particular substrate
↑ Concentration is needed to achieve ½ Vmax
(3) Examples
↓ Km (i) Sarin
Equilibrium is changed (shifted to the right)
Nerve gas
ESI formation → ↓ ES complex formation → reaction
Used in chemical warfare
shifts to the right (by Le Chatelier’s principle) → ↓
Inhibits acetylcholinesterase
substrate concentration → ↓ Km
o Acetylcholinesterase – breaks down acetylcholine
(ii) Aspirin
Irreversible cyclooxygenase (COX) inhibitor
COX – catalyzes the formation of prostaglandins
and leukotrienes [Harvey & Ferrier, 2011]
(3) Examples
(i) Arsenic
Poison
Inhibit glyceraldehyde-3-phosphate dehydrogenase
(G3PDH)
o G3PDH – converts glyceraldehyde-3-phosphate to
1,3-bisphosphoglycerate
(ii) Lithium
Inhibits an enzyme in the phosphoinositide pathway
↓ ↓ -
(iii) Vmax Normal
VI) REFERENCES
1. ENZYME INHIBITION
Enzyme Inhibition: Reversible and Irreversible Inhibition Medical Editor: Jona Frondoso
QUESTIONS ANSWERS
2) Which of the following statements is correct about Correct answer = D. Increases Km. Normal Vmax. Forms
competitive inhibition? noncovalent bonds with the active site.
a) Reduces Km
b) Increases Vmax
c) Forms covalent bonds with the active site
d) Example are statins
3) Which of the following statements is correct about Correct answer = A. Decreases Vmax. ACE inhibitors are
noncompetitive inhibition? examples of competitive inhibitors; Examples of
a) Unchanged Km noncompetitive inhibitors are MAO inhibitors and oxamic acid.
b) Increases Vmax Binds to the allosteric site of either the free enzyme or the ES
c) Examples are ACE inhibitors complex.
d) Binds only to the allosteric site of the ES complex
4) Which of the following statements is correct about Correct answer = B. Decreases Km. MAO-I are examples of
uncompetitive inhibition? noncompetitive inhibitors; Examples of uncompetitive
a) Increases Km inhibitors are arsenic and lithium. Binds only to the allosteric
b) Decreases Vmax site of the ES complex.
c) Examples are MAO-I
d) Binds to the allosteric site of either the free enzyme or
the ES complex