Inhibition of aldehyde dehydrogenase by propiolaldehyde, a possible metabolite of pargyline.

Pargyline (Eutonyl) inhibited aldehyde dehydrogenase (AlDH) in vivo in rats as adduced by the elevation of ethanol-derived blood acetaldehyde (AcH), but had no effect in vitro on the enzyme in intact mitochondria. SKF-525A, an inhibitor of the hepatic microsomal P-450 enzyme system, completely prevented the pargyline-induced elevation of blood AcH in vivo, further implicating a metabolite of pargyline as the active inhibitor of AlDH. Of the potential pargyline metabolites tested, N-benzylpropargylamine and propargyl alcohol--like pargyline itself--readily inhibited AlDH in vivo but were without effect on the enzyme in vitro. These data implicated propiolaldehyde, a theoretically possible product of metabolism of all three of the above compounds, as the active metabolite responsible for AlDH inhibition. Indeed, propiolaldehyde at a concentration of 200 micron essentially completely inhibited the low Km AlDH of intact rat liver mitochondria.