Mechanism of action of allopurinol: September 2005

Ans. A: Inhibits the synthesis of uric acid Allopurinol is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and is an enzyme inhibitor, inhibiting xanthine oxidase. Xanthine oxidase is responsible for the successive oxidation of hypoxanthine and xanthine resulting in the production of uric acid, the product of human purine metabolism. In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine, which are conveed to closely related purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides cause feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol therefore decreases both uric acid formation and purine synthesis.