Abstract
The high xanthine (X) plasma concentration and urine excretion relatively to hypoxanthine (H) in xanthinuric patients, as well as the strong rise of X plasma concentration directly after i.v. allopurinol injection in healthy subjects, might reflect considerable guanine (G) breakdown.
Urate (U), H and X were measured in consecutive plasma and urine specimens before and after an i.v. allopurinol bolusinjection (17.1 μmol/kg body mass) in 8 healthy individuals. The relative importance of the G-X pathway as compared to the H-X pathway in normal unperturbated purine catabolism was estimated from the initial slope of the concentration-time curves and the excretion data. The calculations include the following assumptions: I) an average extrarenal urate elimination rate equal to 35% of the total urate elimination rate, II) a distribution volume equal to 65% of body mass for H and X and III) complete inhibition of the conversion of H to X and of X to U from 5 to 20 min after allopurinol injection, due to high allopurinol and oxypurinol plasma concentrations.
The deamination of G to X was this way estimated to stand for 85 ± 30% (x̄ ± SD) of the X production in unperturbated metabolic state. This does not exclude, however, that the conversion of H to X can be of dominant importance in a state with fast purine catabolism and H accumulation, e.g. hypoxia.
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Van Waeg, G., Niklasson, F. & De Verdier, CH. DEAMINATION OF GUANINE TO XANTHINE: A METABOLIC PATHWAY OF UNDERESTIMATED IMPORTANCE IN HUMAN PURINE CATABOLISM?: 221. Pediatr Res 19, 780 (1985). https://doi.org/10.1203/00006450-198507000-00241
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DOI: https://doi.org/10.1203/00006450-198507000-00241
