Abstract
Of the family of P-450 cytochromes occurring in rabbit liver microsomes, only isozyme 3 a (P-450ALC) is induced by alcohol administration and is effective in catalyzing the reaction: ethanol+02+NADPH+H+ → acetaldehyde +2H2O+NADP+. As judged by immuno-chemical quantitation, P-450ALC is also induced in the animals by other diverse agents, including imidazole, trichlorethylene, acetone, pyrazole, and isoniazid. Evidence has been obtained for the occurrence of a protein immuno-chemically related to P-450ALC in human liver microsomes and of a similar alcohol-inducible protein in the rat and in the normal and alcohol dehydrogenase-deficient deer-mouse. P-450ALC catalyzes the activation of foreign compounds such as acetaminophen, various nitrosamines, and carbon tetrachloride and is therefore believed to play an important role in the enhanced toxicity of these substances accompanying alcohol administration
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Adesnik M, Bar-Nun S, Maschio F, Zunich M, Lippmann A, Bard E (1981) Mechanism of induction of cytochrome P-450 by phenobarbital. J Biol Chem 256: 10340–10345
Coon MJ, Koop DR (1985) Role of alcohol P-450 oxygenase (APO) in microsomal ethanol oxidation. Alcohol 2: 23–36
Domin BA, Serabjit-Singh CJ, Philpot RM (1984) Quantitation of rabbit cytochrome P-450, form 2, in microsomal preparations bound directly to nitrocellulose paper using a modified peroxidase-immunostaining procedure. Anal Biochem 136: 390–396
English JC, Anders MW (1985) Evidence for the metabolism of N-nitrosodimethylamine and carbon tetrachloride by a common isozyme of cytochrome P-450. Drug Metab Disp 13: 449–452
Gorsky LD, Koop DR, Coon MJ (1984) On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem 259: 6812–6817
Johansson I, Ingelman-Sundberg M (1985) Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450. FEBS Lett 183: 265–269
Kokkinakis DM, Koop DR, Scarpelli DG, Coon MJ, Hollenberg PF (1985) Metabolism of N-nitroso-2,6-dimethylmorpholine by isozymes of rabbit liver microsomal cytochrome P-450. Cancer Res 45: 619–624
Koop DR, Casazza JP (1985) Identification of ethanol-inducible P-450 isozyme 3 a as the acetone and acetol monooxygenase of rabbit microsomes. J Biol Chem 260: 13607–13612
Koop DR, Coon MJ (1984) Purification of liver microsomal cytochrome P-450 isozymes 3 a and 6 from imidazole-treated rabbits. Evidence for the identity of isozyme 3 a with the form obtained by ethanol treatment. Mol Pharmacol 25: 494–501
Koop DR, Morgan ET, Tarr GE, Coon MJ (1982) Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits. J Biol Chem 257: 8472–8480
Koop DR, Nordblom GD, Coon MJ (1984) Immunochemical evidence for a role of cytochrome P-450 in liver microsomal ethanol oxidation. Arch Biochem Biophys 235: 228–238
Koop DR, Crump BL, Nordblom GD, Coon MJ (1985) Immuno-chemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid. Proc Natl Acad Sci USA 82: 4065–4069
Lieber CS, DeCarli LM (1970) Hepatic microsomal ethanol-oxidizing system. In vitro characteristics and adaptive properties in vivo. J Biol Chem 245: 2505–2512
Lieber CS, Seitz HK, Garro AJ, Worner TM (1979) Alcohol-related diseases and carcinogenesis. Cancer Res 39: 2863–2886
McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL (1980) Potentiation of acetaminophen toxicity by alcohol. JAMA 244: 251–253
Mezey E (1976) Ethanol metabolism and ethanol-drug interaction. Biochem Pharmacol 25: 869–875
Morgan ET, Koop DR, Coon MJ (1982) Catalytic activity of cytochrome P-450 isozyme 3 a isolated from liver microsomes of ethanol-treated rabbits. J Biol Chem 257: 13951–13957
Morgan ET, Koop DR, Coon MJ (1983) Comparison of six rabbit liver cytochrome P-450 isozymes in formation of a reactive metabolite of acetaminophen. Biochem Biophys Res Commun 112: 8–13
Morville AL, Thomas P, Levin W, Reik L, Ryan DE, Raphael C, Adesnik M (1983) The accumulation of distinct mRNAs for the immunochemically related cytochromes P-450c and P-450d in rat liver following 3-methylcholanthrene treatment. J Biol Chem 258: 3901–3906
Proudfoot AT, Wright N (1970) Acute paracetamol poisoning. Br Med J 3: 557–558
Smith AC, Freeman RN, Harbison RD (1981) Ethanol enhancement of cocaine-induced hepatotoxicity. Biochem Pharmacol 30: 451–453
Traiger GJ, Plaa GL (1972) Relationship of alcohol metabolism to the potentiation of CCl4 hepatotoxicity induced by aliphatic alcohols. J Pharmacol Exp Ther 183: 481–488
Yang CS, Tu YY, Koop DR, Coon MJ (1985a) Metabolism of nitrosamines by purified rabbit liver cytochrome P-450 isozymes. Cancer Res 45: 1140–1145
Yang CS, Koop DR, Wang T, Coon MJ (1985b) Immunochemical studies on the metabolism of nitrosamines by ethanol-inducible cytochrome P-450. Biochem Biophys Res Commun 128: 1007–1013
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Dedicated to Professor Dr. Herbert Remmer on the occasion of his 65th birthday
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Coon, M.J., Koop, D.R. Alcohol-inducible cytochrome P-450 (P-450ALC). Arch Toxicol 60, 16–21 (1987). https://doi.org/10.1007/BF00296940
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DOI: https://doi.org/10.1007/BF00296940