Hypoxanthine analogue allopurinol

In most patients with gout as well as those with Lesch-Nyhan syndrome, purines are overproduced and overexcreted. Yet the hypoxanthine analogue allopurinol, which effectively treats gout, has no effect on the severe neurological symptoms of Lesch-Nyhan patients because it does not... 

Hyperuricemia can be treated with allopurinol, a competitive inhibitor of xanthine oxidase. This substrate analogue differs from the substrate hypoxanthine only in the arrangement of the atoms in the 5-ring. 

Certain drugs inhibit non-microsomal metabolic pathways. Metronidazole, like disulfiram, inhibits aldehyde dehydrogenase, the enzyme that normally oxidizes acetaldehyde to acetic acid in the metabolic pathway for ethanol. Allopurinol inhibits xanthine oxidase, the enzyme that catalyses the oxidation of hypoxanthine to xanthine and xanthine to uric acid. Because azathioprine and 6-mercaptopurine are metabolized by xanthine oxidase, the dosage of these drugs (synthetic xanthine analogues), when used concomitantly with... 

Allopurinol, a structural analogue of hypoxanthine, is a competitive inhibitor as well as a substrate for xanthine oxidase ... 

Allopurinol, an analogue of hypoxanthine, inhibits xanthine oxidase and reduces formation of xanthine and uric acid. It is converted by xanthine oxidase to alloxanthine, which binds tightly to the active site by chelation with... 

The answer is d. (Murray, pp 375-401. Scriver, pp 2513-2570. Sack, pp 121-138. Wilson, pp 287-320.) Xanthine oxidase catalyzes the last two steps in the degradation of purines. Hypoxanthine is oxidized to xanthine, and xanthine is further oxidized to uric acid. Thus, xanthine is both product and substrate in this two-step reaction. In humans, uric acid is excreted via the urine. Allopurinol, an analogue of xanthine, is used in gout to block uric acid production and deposition of uric acid crystals in the kidneys and joints. It acts as a suicide inhibitor of xanthine oxidase after it is converted to alloxanthine. Guanine can also be a precursor of xanthine. 

It may be prepared by the interaction of hypoxanthine with phosphorus pentasulphide. Mercaptopurine is found to inhibit experimental orthoimmune encephalomyletis and thyroiditis and hence used in combination with vincristine, methortrexate and prednisone in the treatment of childhood leukemia. As such 6-MP may cause hyperuricamia but it is usually administered with allopurinol—an analogue of hypoxanthine which blocks the conversion of 6-MP to uric acid and hence the dose of 6-MP is reduced and still the desired response is obtained. 

Pyrazolopyrimidines are purine analogues in which the nitrogen and carbon of the imidazole ring are inverted. The best known member of this group, allopurinol (4-hydroxypyrazolo(3,4-d)pyrimidine HPP), is a structural analogue of hypoxanthine. Its major metabolic conversions in mammalian cells are to oxipurinol, via xanthine oxidase, and to allopurinol ribonucleoside (HPPR)l. 

Allopurinol is a structural analogue of hypoxanthine and as such inhibits xanthine oxidase and the oxidation of hypoxanthine to xanthine and xanthine to uric acid (Feigelson, Davidson and Robins,... 

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