Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients.
Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients.
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对嘌呤核苷磷酸化酶和次黄嘌呤鸟嘌呤磷酸核糖基转移酶缺陷患者中 S-腺苷同型半胱氨酸水解酶缺陷的拟议解释。
DOI：
10.1172/jci110085
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Hershfield,MS
中科院分区：
文献类型：
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作者：
Hershfield,MS
我们研究了最近报道的，但无法解释的，嘌呤核苷磷酸化酶和次黄嘌呤-鸟嘌呤磷酸化核糖转移酶遗传缺陷患者红细胞中s -腺苷同型半胱氨酸水解酶（AdoHcyase）缺乏的基础。我们发现嘌呤核苷磷酸化酶缺乏症患者的溶血液只有7%的对照AdoHcyase活性，符合最初的观察结果。已知嘌呤核苷在核苷磷酸化酶缺陷患者中积累，肌苷单独引起纯化的人胎盘AdoHcyase和完整红细胞和培养的淋巴母细胞样细胞中AdoHcyase的磷酸依赖性、不可逆失活。次黄嘌呤不会使纯化的AdoHcyase失活，但会增强肌苷对完整的次黄嘌呤-鸟嘌呤磷酸核糖基转移酶缺陷的人淋巴母细胞样细胞的作用。这可能是由于次黄嘌呤能够改变核苷磷酸化酶反应的平衡，从而防止肌苷分解。这可以解释在次黄嘌呤-鸟嘌呤磷酸核糖基转移酶缺乏的患者中报告的部分AdoHcyase缺乏。我们还证明了adohycase催化从肌苷和l -同型半胱氨酸合成s -肌苷同型半胱氨酸，这一反应可能发生在核苷磷酸化酶缺乏的患者中。
We have examined the basis for the recently reported, but unexplained deficiency of S-adenosylhomocysteine hydrolase (AdoHcyase) in the erythrocytes of patients with genetic deficiencies of purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase. We found that a hemolysate from a patient with purine nucleoside phosphorylase deficiency had only 7% of control AdoHcyase activity, conforming the original observation. Of the purine nucleosides known to accumulate in nucleoside phosphorylase-deficient patients, inosine alone caused the phosphate-dependent, irreversible inactivation of purified human placental AdoHcyase, and of AdoHcyase in intact erythrocytes and cultured lymphoblastoid cells. Hypoxanthine did not inactivate purified AdoHcyase, but potentiated the effect of inosine in intact hypoxanthine-guanine phosphoribosyltransferase-deficient human lymphoblastoid cells. This presumably resulted from the ability of hypoxanthine to shift the equilibrium of the nucleoside phosphorylase reaction, preventing inosine breakdown. This could account for the partial AdoHcyase deficiency reported in hypoxanthine-guanine phosphoribosyltransferase-deficient patients. We have also demonstrated the AdoHycase-catalyzed synthesis of S-inosylhomocysteine from inosine and L-homocysteine, a reaction which may occur in nucleoside phosphorylase-deficient patients.