Aldehyde dehydrogenase activity as the rate-limiting factor for acetaldehyde metabolism in rat liver

• Published in: Archives of biochemistry and biophysics Vol. 236; no. 1; pp. 36 - 46
• Main Authors: Svanas, Gregory W., Weiner, Henry
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 1985; Elsevier
• Subjects: Acetaldehyde - metabolism; Aldehyde Dehydrogenase - antagonists & inhibitors; Aldehyde Dehydrogenase - metabolism; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cyanamide - pharmacology; Electron Transport; Enzymes and enzyme inhibitors; Ethanol - metabolism; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Kinetics; Liver - metabolism; Male; Mitochondria, Liver - enzymology; NAD - metabolism; Oxidation-Reduction; Oxidoreductases; Rats; Rats, Inbred Strains; Rat; Enzyme; Liver; Rodentia; Metabolism; Aldehyde dehydrogenase; Fluorescence spectrometry; Acetaldehyde; Vertebrata; Mitochondria; Mammalia; Limiting factor; Kinetic parameter; Catalyst activity
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/0003-9861(85)90603-4

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- K m ALDH in slices or intact mitochondria was partially inhibited by treatment with cyanamide and the rate of acetaldehyde metabolism measured. Any inhibition of low- K m ALDH resulted in a decreased rate of acetaldehyde metabolism, indicating that no excess of low- K m ALDH existed. Approximately 40% of the metabolism of 200 μ m acetaldehyde in slices was not catalyzed by low- K m ALDH. Fifteen of this 40% was catalyzed by high- K m ALDH. A possible contribution by aldehyde oxidase was ruled out through the use of a competitive inhibitor, quinacrine. Acetaldehyde binding to cystosolic proteins may account for the remainder. By measuring acetaldehyde accumulation during ethanol metabolism, it was also established that low- K m ALDH activity was rate-limiting for acetaldehyde oxidation during concomitant ethanol oxidation.