Aldehyde dehydrogenase activity as the rate-limiting factor for acetaldehyde metabolism in rat liver.
The velocity of acetaldehyde metabolism in rat liver may be governed either by the rate of regeneration of NAD from NADH through the electron transport system or by the activity of aldehyde dehydrogenase (ALDH). Measurements of oxygen consumption revealed that the electron transport system was capable of reoxidizing ALDH-generated NADH much faster than it was produced and hence was not rate-limiting for aldehyde metabolism. To confirm that ALDH activity was the rate-limiting factor, low-Km ALDH in slices or intact mitochondria was partially inhibited by treatment with cyanamide and the rate of acetaldehyde metabolism measured. Any inhibition of low-Km ALDH resulted in a decreased rate of acetaldehyde metabolism, indicating that no excess of low-Km ALDH existed. Approximately 40% of the metabolism of 200 microM acetaldehyde in slices was not catalyzed by low-Km ALDH. Fifteen of this 40% was catalyzed by high-Km ALDH. A possible contribution by aldehyde oxidase was ruled out through the use of a competitive inhibitor, quinacrine. Acetaldehyde binding to cytosolic proteins may account for the remainder. By measuring acetaldehyde accumulation during ethanol metabolism, it was also established that low-Km ALDH activity was rate-limiting for acetaldehyde oxidation during concomitant ethanol oxidation.
D000079:Acetaldehyde / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology; D004579:Electron Transport; D000431:Ethanol / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D009243:NAD; D000431:Ethanol; D003484:Cyanamide; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde