Effects of acetaldehyde on human red cell metabolism: evidence for the formation of enzyme inhibitors.
Since red cells transport and metabolize acetaldehyde in vivo, the effects of acetaldehyde on human red cell enzyme activities were studied. Incubation of intact red cells or undiluted red cell lysates at 37 degrees C for 4 h with 1-10 mmol/l acetaldehyde decreased only GOT, GPT and aldolase activities among the 26 enzymes tested. No inhibition occurred at 4 degrees C or when acetaldehyde was incubated with dilute hemolysates. Incubation of lysates with other reducing substrates or with acetate inhibited aldolase but not GOT or GPT. Preincubation of lysates with cyanate or fluoride markedly decreased acetaldehyde-mediated transaminase inhibition but not aldolase inhibition. Addition of pyridoxal phosphate, the vitamin B6 transaminase coenzyme, to GOT and GPT assay mixes did not reverse acetaldehyde-mediated transaminase inhibition. These findings suggest that acetaldehyde-mediated aldolase inhibition results from oxidation of acetaldehyde while transaminase inhibition results from nonoxidative acetaldehyde metabolism. When 100-200 mumol/l acetaldehyde is added to lysates at 2-h intervals and when lysates are incubated with ethanol, alcohol dehydrogenase and an NAD-regenerating system, enzyme inhibition occurs at acetaldehyde levels approaching those seen in vivo. Thus, the role of acetaldehyde-mediated enzyme inhibition in the toxicity of alcohol abuse warrants further study.
Department of Medicine, Veterans Administration Medical Center, West Haven, CT 06516.
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Solomon
D000079:Acetaldehyde / Q000097:blood / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000097:blood; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005634:Fructose-Bisphosphate Aldolase; D000079:Acetaldehyde