Human mitochondrial aldehyde dehydrogenase inhibition by diethyldithiocarbamic acid methanethiol mixed disulfide: a derivative of disulfiram

FEBS Letters

Pietruszko, Regina¹  Vallari, Robert C.¹  MacKerell, Alexander D.¹ 

[1] Center of Alcohol Studies, Rutgers University, New Brunswick, NJ 08903, USA

关键词: Mitochondrial aldehyde dehydrogenase;    Disulfiram;    Diethyldithiocarbamic acid methanethiol mixed disulfide;   

DOI  :  10.1016/0014-5793(85)80195-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A derivative and possible physiological metabolite of disulfiram, diethyldithiocarbamic acid methanethiol mixed disulfide, is shown here for the first time to inactivate the mitochondrial low-K _m, isozyme of human aldehyde dehydrogenase (EC 1.2.1.3). By comparing inactivating effects of diethyldithiocarbamic acid mixed disulfides with thiols of increasing chain length evidence is provided that steric hindrance is the reason for lack of inhibition of the mitochondrial enzyme by disulfiram in vitro. Since methanethiol is a normal metabolite [(1983) Annu. Rev. Biochem. 52, 187–222] the results also suggest a mechanism by which aldehyde dehydrogenase is inhibited by disulfiram and diethyldithiocarbamic acid in vivo.

【 授权许可】

Unknown