Study on Biochemical Abnormalities of Congenital organic aciduria

我们研究了多种羧化酶缺乏症、酮症高甘氨酸血症、甲基戊烯二酸尿症和乳酸中毒的生化异常。1）多种羧化酶缺乏症：发现患者的成纤维细胞和白细胞具有ACC（胞浆酶）以及PCC、MCC和PC（线粒体酶）的缺乏。我们认为，这种疾病的主要缺陷是在全羧化酶合成酶。2)酮症高甘氨酸血症：我们认为，酮症高甘氨酸血症时肝脏甘氨酸裂解系统的降低是继发性的，主要是由H蛋白活性降低引起的。3)甲基戊烯二酸尿症：我们开发了一种新的测定3-甲基戊烯二酰辅酶A水合酶的方法，其中底物[5- <^（14）C> ]3-甲基戊烯二酰辅酶A使用3-甲基巴豆酰辅酶A羧化酶合成。两例患者的酶活性为正常值的2[3%]。4)乳酸酸中毒：对56例乳酸酸中毒患者的培养皮肤成纤维细胞进行酶研究。其中8例为丙酮酸脱羧酶（PDC）缺乏，6例为细胞色素c氧化酶减少。提示PDC严重缺乏者易发生Leigh病，而PDC轻度缺乏者不一定发生Leigh病。两个兄弟姐妹与细胞色素c氧化酶缺乏症被诊断为利氏病，似乎是第一个案件的细胞色素c氧化酶的全面缺陷。

We studied on biochemical abnormalities of multiple carboxylase deficiency, ketotic hyperglycinemia ,methylglutaconic aciduria and lactic acidosis.1)Multiple carboxylase deficiency: Fibroblasts and leukocytes from the patient were found to have a deficiency of ACC,cytosolic enzyme,as well as PCC,MCC and PC, which are mitochondrial enzymes. We suggested that the primary defect in this disorder was in the holocarboxylase synthetase. 2) Ketotic hyperglycinemia : We suggested that the reduction of the glycine cleavage system in the liver of ketotic hyperglycinemia occured secondarily and was caused mainly by a decrease of H-protein activity. 3) Methylglutaconic aciduria : We developed a new assay for 3 methylglutaconyl CoA hydratase in which the substrate,[5- <^(14)C> ]3-methylglutaconyl CoA,was synthesized using 3 methylcrotonyl CoA carboxylase. In the two patients the enzyme activities were 2[3% of normal. 4) Lactic acidosis: An enzymatic study of cultured skin fibroblasts was 56 patoents with lactic acidosis. In eight of the patients pyruvate decarboxylase (PDC) deficiency was found. The reduction of cytochrome c oxidase was demonstrated in six of the patients. It was suggested that the patients with severe PDC deficiency developed Leigh's disease but those with mild deficiency might not. Two siblings with cytochrome c oxidase deficiency was diagnosed as having Leigh's disease and seemed to be the first case of a generalized defect in cytochrome c oxidase.