Inhibition of rat liver aldehyde dehydrogenases by acrolein.
Acrolein, the lowest member of the ethylenic aldehyde series, has been widely studied as a result of the diverse toxicities associated with it. Previous investigations into the enzymatic process responsible for the detoxification of acrolein implicated rat liver aldehyde dehydrogenase (ALDH) in the oxidation of this aldehyde. Contrary to these reports, in our investigation we were unable to detect the oxidation of acrolein to acrylic acid by Sprague-Dawley rat liver mitochondrial or cytosolic ALDHs measured spectrophotometrically by the production of NADH, or by HPLC analysis for the production of acrylic acid. However, in the course of these experiments, it was demonstrated that acrolein is a potent inhibitor of rat liver ALDHs. Mitochondrial and cytosolic high affinity ALDHs are particularly sensitive to the inhibitory effects of acrolein. The type of inhibition exhibited by these high affinity ALDHs is primarily irreversible, with a slight degree of reversible noncompetitive inhibition. The inhibition is rapid with a 91 and 33% reduction in control mitochondrial and cytosolic ALDH activities, respectively, with a 5-sec preincubation of 30 microM acrolein prior to the addition of the aldehyde substrate. Significant inhibition of total (high plus low affinity isozymes) mitochondrial and cytosolic ALDHs occurs only at relatively high acrolein concentrations (greater than or equal to 50 microM). The inhibition displayed by the total mitochondrial and cytosolic ALDHs is mixed-type, with both reversible noncompetitive and irreversible inhibition demonstrated.
D000171:Acrolein / Q000494:pharmacology*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology
D000447:Aldehydes; D008623:Mercaptoethanol; D000171:Acrolein; D000444:Aldehyde Dehydrogenase