琥珀酸半醛脱氢酶缺乏症：一种γ-氨基丁酸代谢的先天性疾病。

Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism.

作者信息

Gibson K M, Sweetman L, Nyhan W L, Jakobs C, Rating D, Siemes H, Hanefeld F

出版信息

Clin Chim Acta. 1983 Sep 15;133(1):33-42. doi: 10.1016/0009-8981(83)90018-9.

Abstract

Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 +/- 1.9 pmol . min-1 . mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol . min-1 . mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.

摘要

γ-羟基丁酸尿症是一种γ-氨基丁酸代谢紊乱疾病，其中一种具有已知神经药理活性的化合物会蓄积。我们研究了两名患者，他们的血液、尿液和脑脊液中均发现了高水平的γ-羟基丁酸。我们开发了一种偶联测定法，用于估计分离出的人淋巴细胞中的琥珀酸半醛脱氢酶活性。这些患者的一名对照者以及四名父母和两名健康同胞中，琥珀酸半醛脱氢酶的平均活性为8.8±1.9 pmol·min⁻¹·mg⁻¹蛋白质。而患者的活性分别为0.8和1.1 pmol·min⁻¹·mg⁻¹蛋白质，约为对照者的9% - 13%。在存在饱和量NAD⁺的情况下，患者来源的淋巴细胞超声裂解物会从¹⁴C-γ-氨基丁酸中积累大量¹⁴C-琥珀酸半醛，而对照者中未检测到。数据表明这些患者存在琥珀酸半醛脱氢酶缺乏，这是人类γ-氨基丁酸代谢中首个有记录的缺陷。