Treatment of Gout Allopurinol, an inhibitor of xanthine oxidase, is used to trea

Question

Treatment of Gout

Allopurinol, an inhibitor of xanthine oxidase, is used to treat chronic gout. At this point you should be looking at the

degradation pathway for purines in your notes.

a.

Copy the structure of allopurinol from the class notes.

b. What is the chemical basis for this treatment?

c. Patients treated with allopurinol sometimes develop xanthine stones in the kidneys. Explain this observation in

the light of the following solubilities in urine: uric acid, 0.15 g/L; xanthine, 0.05 g/L; and hypoxanthine, 1.4 g/L.

Explanation / Answer

Solution:

Ans) High level of uric acid or urate (hyperuricemia) level induces the painful joint disease called Gout. Administration of allopurinol, an analog of hypoxanthine is one of the way for the treatment of Gout. This is because llopurinol first acts as a substrate and then acts as an inhibitor of the enzyme xanthine oxidase. The enzyme Hypoxanthine oxidase binds the allopurinol instreat of its substrate hypoxanthine and convert the allopurinol to alloxanthine. This alloxanthine binds tightly to the active site of the xanthine oxidase and remain bound with the enzyme. Thus it block the activity of the enzyme for further progress. This type of inhibition is called suicide inhibitor. The synthesis of urate from xanthine and hypoxanthine decrease soon after the administration of the allopurinol. The serum concentration of hpoxanthine and xanthine rises and that of uric acid drops.

From the given observation it observed that the level of hypoxanthine is high in compared to uric acid and xanthine after the administartion of the allopurinol. Hpoxanthine is complex macromolecular and due to the suicide inhibitor acivity of the allopurinol on hypoxanthine oxidase, there is accumulation of hypoxanthine in the blood. Due to its macromolecular nature it is not filtered through the kidney and thus deposited in the glomerulus to form stones.

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