Cohen A, Doyle D, Martin D W, Ammann A J
N Engl J Med. 1976 Dec 23;295(26):1449-54. doi: 10.1056/NEJM197612232952603.
To delineate the normal function of purine nucleoside phosphorylase and to understand the pathogenesis of the immune dysfunction associated with deficiency of this enzyme, we studied purine metabolism in a patient deficient in purine nucleoside phosphorylase, her erythrocytes and cultured fibroblasts. She exhibited severe hypouricemia and hypouricosuria but excreted excessive amounts of purines in her urine, the major components of which were inosine and guanosine. Her urine also contained deoxyinosine, deoxyguanosine and uric acid 9-N riboside. The patient's erythrocytes but not her cultured fibroblasts contained increased concentrations of phosphoribosylpyrophosphate and inosine. The metabolic abnormalities resembled those in the erythrocytes of patients with the Lesch-Nyhan syndrome. Purine nucleoside phosphorylase is a necessary component of the major, if not the sole, pathway for the conversion of purine nucleosides and nucleotides to uric acid. The increased intracellular concentrations of inosine may, by inhibiting adenosine deaminase, be related to the immunologic dysfunction.
为了阐明嘌呤核苷磷酸化酶的正常功能，并了解与该酶缺乏相关的免疫功能障碍的发病机制，我们研究了一名嘌呤核苷磷酸化酶缺乏患者、她的红细胞和培养的成纤维细胞中的嘌呤代谢。她表现出严重的低尿酸血症和低尿酸尿症，但尿中排出过量的嘌呤，其中主要成分是肌苷和鸟苷。她的尿液中还含有脱氧肌苷、脱氧鸟苷和尿酸9-N核糖苷。患者的红细胞而非培养的成纤维细胞中磷酸核糖焦磷酸和肌苷的浓度升高。这些代谢异常与莱施-奈恩综合征患者红细胞中的异常相似。嘌呤核苷磷酸化酶是嘌呤核苷和核苷酸转化为尿酸的主要（如果不是唯一）途径的必要组成部分。肌苷细胞内浓度的增加可能通过抑制腺苷脱氨酶而与免疫功能障碍有关。
