The microsomal ethanol oxidizing system: its role in ethanol and xenobiotic metabolism.
After chronic ethanol consumption, the activity of the microsomal ethanol-oxidizing system (MEOS) increases and contributes to ethanol tolerance, as most conclusively shown in alcohol-dehydrogenase-negative deermice. In man and animals, there is an associated rise in microsomal cytochrome P-450, including a specific form (P-450IIEI) with high affinity for ethanol and for the activation of some drugs (i.e. acetaminophen), carcinogens (i.e. N-nitrosodimethylamine) and hepatotoxic agents (i.e. CCl4), thereby contributing to the susceptibility of alcoholics to xenobiotics, including industrial solvents. In addition, a benzoflavone-inducible liver cytochrome P-450 isoenzyme distinct but catalytically similar to cytochrome P-450IIE1 was purified which may play a significant role in drinkers who also are heavy smokers. Cross-induction of other microsomal enzymes is associated with enhanced metabolism of various drugs, resulting in drug tolerance. Catabolism of retinol was also found to be accelerated, in part through activation of newly discovered vitamin A depletion and possibly toxicity. Thus, elucidation of the microsomal metabolism of ethanol explains a number of complications that develop in alcoholics.
Lieber
C S
CS
Alcohol Research and Treatment Center, Veterans Administration Medical Center, Bronx, New York.
D000595:Amino Acid Sequence; D000818:Animals; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D013256:Steroids / Q000378:metabolism; D014815:Vitamins / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism*
D013256:Steroids; D014815:Vitamins; D015262:Xenobiotics; D000431:Ethanol