Raivio K O, Becker 7 A, Meyer L J, Greene M L, Nuki G, Seegmiller J E
Metabolism. 1975 Jul;24(7):861-9. doi: 10.1016/0026-0495(75)90133-x.
In order to clarify the mechanism of hyperuricemia and hyperuricosuria resulting from rapid infusion of fructose in man, the effects of an intravenous infusion of 125-200 g of fructose given over 3-4 hr on the rate of purine synthesis de novo was measured in one individual with osteoarthritis and four patients with gout. The incorporation of 1-minus 14C glycine into urinary uric acid was measured, and the pool size and turnover of urate were assessed by renal excretion of simultaneously administered 15-N urate. Fructose caused an expansion of body urate pool in all subjects, while urate turnover was increased in four. The rate of incorporation of 14-C glycine into urinary uric acid corrected for extrarenal disposal was increased in all cases (21%-430%). In two patients, rates of incorporation of 14-C glycine into urinary creatinine were increased by 10% and 11%, while rates of incorporation into uric acid were increased 84% and 159%, respectively, as a result of fructose infusion. Specific enhancement of the rate of purine synthesis de novo was suggested by these findings. The rate of infusion appeared more important than total dose in determining the magnitude of this effect. Whether the increased rate of purine synthesis was a result of direct stimulation by a fructose metabolite or was secondary to fructose-induced purine nucleotide depletion is uncertain, since the kinetics of glycine incorporation were consistent with either mechanism. Erythrocyte PP-ribose-P concentrations, however, were diminished during infusion rather than increased as might be expected if fructose infusion stimulated purine synthesis by increasing availability of this regulatory substrate.
为了阐明人体快速输注果糖导致高尿酸血症和高尿酸尿症的机制，在1例骨关节炎患者和4例痛风患者中，测量了在3 - 4小时内静脉输注125 - 200克果糖对嘌呤从头合成速率的影响。测量了1 - 14C甘氨酸掺入尿尿酸的情况，并通过同时给予的15 - N尿酸的肾脏排泄来评估尿酸盐池大小和周转率。果糖使所有受试者的体内尿酸盐池扩大，而4例受试者的尿酸盐周转率增加。校正肾外排泄后，所有病例中14 - C甘氨酸掺入尿尿酸的速率均增加（21% - 430%）。在2例患者中，果糖输注后，14 - C甘氨酸掺入尿肌酐的速率分别增加了10%和11%，而掺入尿酸的速率分别增加了84%和159%。这些发现提示嘌呤从头合成速率有特异性增强。在决定这种效应的大小时，输注速率似乎比总剂量更重要。嘌呤合成速率增加是果糖代谢产物直接刺激的结果，还是继发于果糖诱导的嘌呤核苷酸耗竭尚不确定，因为甘氨酸掺入的动力学与这两种机制均相符。然而，输注期间红细胞PP - 核糖 - P浓度降低，而不是像果糖输注通过增加这种调节底物的可用性来刺激嘌呤合成时所预期的那样升高。
