Further characterization of the inhibition of aldehyde dehydrogenase activity by pargyline.
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.
D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D010293:Pargyline / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D013997:Time Factors
D010293:Pargyline; D000445:Aldehyde Oxidoreductases; D010634:Phenobarbital