DEFECTIVE GLYCINE CLEAVAGE SYSTEM IN NON-KETOTIC HYPERGLYCINEMIA - OCCURRENCE OF A LESS ACTIVE GLYCINE DECARBOXYLASE AND AN ABNORMAL AMINOMETHYL CARRIER PROTEIN
DEFECTIVE GLYCINE CLEAVAGE SYSTEM IN NON-KETOTIC HYPERGLYCINEMIA - OCCURRENCE OF A LESS ACTIVE GLYCINE DECARBOXYLASE AND AN ABNORMAL AMINOMETHYL CARRIER PROTEIN
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DOI：
10.1172/jci110284
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发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
NYHAN, WL
中科院分区：
文献类型：
--
作者：
HIRAGA, K;KOCHI, H;NYHAN, WL
非酮症高甘氨酸血症患者的肝和脑中的甘氨酸裂解系统的活性与对照人肝和脑中的甘氨酸裂解系统的活性相比极低。甘氨酸脱羧酶（P-蛋白）和氨甲基载体蛋白（H-蛋白），2的4个蛋白质组分的甘氨酸裂解系统的活动，大大减少了在肝脏和大脑中，减少的程度更大的H-蛋白。T蛋白活性正常。从患者纯化的H-蛋白不与硫辛酰胺脱氢酶反应，用[2，3 - 14 C] N-乙基马来酰亚胺滴定巯基表明该H-蛋白不含硫辛酸。这种H蛋白的结构异常被认为是构成该非酮症高甘氨酸血症患者的主要分子病变。使用P-蛋白特异性抗体的免疫化学研究表明，观察到的患者P-蛋白活性降低是由于蛋白催化活性降低，而不是P-蛋白实际量减少。P蛋白的部分失活可能是由于甘氨酸代谢受损，导致H蛋白活性不足。病人的H-蛋白能刺激P-蛋白催化的甘氨酸羧基碳与~（14）CO_2的交换，但其比活性仅为对照H-蛋白的4%。患者肝脏中的H蛋白含量为约0.00000。35%的人肝。
The activities of the glycine cleavage system in the liver and brain of a patient with nonketotic hyperglycinemia were extremely low compared with those of control human liver and brain. The activities of glycine decarboxylase (P-protein) and the aminomethyl carrier protein (H-protein), 2 of the 4 protein components of the glycine cleavage system, were considerably reduced in both the liver and brain; the extent of reduction was greater in the H-protein. The activity of the T-protein was normal. Purified H-protein from the patient did not react with lipoamide dehydrogenase, and titration of thiol groups with [2,3-14C]N-ethylmaleimide suggested that this H-protein is devoid of lipoic acid. This structural abnormality in the H-protein is considered to constitute the primary molecular lesion in this patient with nonketotic hyperglycinemia. Immunochemical studies using an antibody specific for P-protein showed that the observed reduction in the activity of the P-protein in the patient was due to reduction of the catalytic activity of the protein rather than a decrease in the actual amount of the P-protein. Partial inactivation of P-protein could result secondarily from impaired metabolism of glycine, resulting from deficiency in the activity of H-protein. The H-protein from the patient could stimulate the P-protein catalyzed exchange of the carboxyl carbon of glycine with 14CO2, although the specific activity of the purified H-protein from the patient was only 4% of that of control human H-protein. The content of H-protein in the liver of the patient was .apprx. 35% of that of control human liver.