Marchner H, Tottmar O
Acta Pharmacol Toxicol (Copenh). 1978 Sep;43(3):219-32. doi: 10.1111/j.1600-0773.1978.tb02258.x.
1-aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH) in vivo and in vitro. Like cyanamide it has a rapid onset of action in vivo with the highest inhibition occurring after 2--24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low-Km ALDH strongly in vivo, however, in markedly different doses. Cyanamide inhibited the high-Km ALDH only in vivo, whereas in vitro, the hihgh-Km ALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low-Km enzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram-ethanol reaction are discussed.
1-氨基环丙醇(ACP)在体内和体外都是醛脱氢酶(ALDH)的有效抑制剂。与氰胺一样,它在体内起效迅速,在2至24小时后抑制作用最强,且作用持续时间长,类似于双硫仑,在144小时后仍有可测量的抑制作用。这三种抑制剂在体内均能强烈降低线粒体低Km ALDH的活性,但所需剂量明显不同。氰胺仅在体内抑制高Km ALDH,而在体外,高Km ALDH不受氰胺影响,但双硫仑和ACP能显著抑制它。这些抑制剂产生的抑制作用似乎是不可逆的。根据所用抑制剂的不同,乙醛对低Km酶有不同程度的保护作用。本文讨论了抑制剂对中毒大鼠和对照大鼠ALDH的抑制作用及其与乙醛氧化和双硫仑-乙醇反应的关系。