[Metabolic aspects of alcoholic liver damage: 1984/1985 update. 2: Microsomal enzyme induction and hypermetabolism].
In the second part of this review, the effect of ethanol on hepatic microsomal enzymes is primarily discussed. Since ethanol is metabolized via a cytochrome P-450 dependent biotransformation system (MEOS) in hepatic microsomes, the microsomal enzyme induction in the smooth endoplasmic reticulum has to be considered as an adaptive response. This enzyme induction results in an accelerated metabolism of ethanol. However, subsequently, the negative consequences of such a microsomal enzyme induction are predominant. Acetaldehyde production increases and oxygen consumption is enhanced leading to pericentral (perivenular) hypoxia. In addition, microsomal enzyme induction results in an enhanced metabolism of drugs, xenobiotics and hepatotoxins and thus to an increased production of toxic intermediates. Also procarcinogens are activated to a higher degree in microsomes following chronic ethanol consumption. Subsequently, an enhanced microsomal metabolism of vitamin A may explain the low serum concentrations of this vitamin in the alcoholic and may lead to toxic metabolites of retinol. The quantitative role of an enhanced reoxidation of NADH responsible for an increased oxidation of alcohol following chronic ethanol ingestion has still to be determined. However, according to recent investigations, a thyroid hormone induced hypermetabolism seems unlikely.
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D000079:Acetaldehyde / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004790:Enzyme Induction; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D050356:Lipid Metabolism; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D009243:NAD; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C019642:alcohol dehydrogenase (NADP+); D005723:gamma-Glutamyltransferase; D000079:Acetaldehyde
Metabolische Aspekte der alkoholischen Leberschädigung: Update 1984/85. Teil 2: Mikrosomale Enzyminduktion und Hypermetabolismus.