Lebsack M E, Anderson A D
Res Commun Chem Pathol Pharmacol. 1979 Nov;26(2):263-75.
The in vivo inhibition of low Km mitochondrial aldehyde dehydrogenase (AlDH) activity by pargyline was not maximal until more than 30 minutes after i.p. injection. Enzyme activity returned to control levels within 36 hours of drug injection but the return of activity was slowed by cycloheximide pretreatment. Female rats and higher basal total and low Km mitochondrial AlDH activities than did males. Injection of pargyline inhibited low Km mitochondrial AlDH activity more in males than in females. Incubation of rat liver microsomes with an NADPH-generating system and pargyline produced an in vitro inhibitor of low Km mitochondrial AlDH activity. Pretreatment of rats with phenobarbital increased the AlDH inhibitor produced by incubation of their microsomes with pargyline. Injection with benzylpropargylamine, N-demethylated pargyline, also preferentially inhibited the low Km form of mitochondrial AlDH activity. Neither pargyline nor benzylpropargylamine injections affected microsomal AlDH activity. Total AlDH activity, measured with 5mM propionaldehyde, in rat liver 100,000g supernatant was not changed by administration of either drug. Supernatant activity assayed with 50 microM propionaldehyde was inhibited by both pargyline and benzylpropargylamine treatment.
优降宁对低 Km 线粒体乙醛脱氢酶（AlDH）活性的体内抑制作用在腹腔注射后 30 多分钟才达到最大。酶活性在药物注射后 36 小时内恢复到对照水平，但环己酰亚胺预处理会减缓活性的恢复。雌性大鼠的基础总 AlDH 活性和低 Km 线粒体 AlDH 活性高于雄性。注射优降宁对雄性低 Km 线粒体 AlDH 活性的抑制作用大于雌性。用产生 NADPH 的系统和优降宁孵育大鼠肝微粒体可产生低 Km 线粒体 AlDH 活性的体外抑制剂。用苯巴比妥预处理大鼠会增加其微粒体与优降宁孵育产生的 AlDH 抑制剂。注射苄基炔丙胺（N - 去甲基优降宁）也优先抑制线粒体 AlDH 活性的低 Km 形式。优降宁和苄基炔丙胺注射均不影响微粒体 AlDH 活性。用 5mM 丙醛测定大鼠肝脏 100,000g 上清液中的总 AlDH 活性，两种药物给药后均未改变。用 50μM 丙醛测定上清液活性时，优降宁和苄基炔丙胺处理均有抑制作用。
