[Ethanol metabolism and pathobiochemistry of organ damage--1992. I. Metabolism of ethanol by alcohol dehydrogenase, cytochrome P450IIE1 and catalase]. 1993

T Zima
I. ústav lékarské chemie a biochemie, 1. lékarská fakulta Univerzity Karlovy, Praha.

Three metabolic pathways of ethanol in human body have been described thus far: 1) alcohol dehydrogenase (ADH), 2) microsomal oxidizing ethanol system (MEOS), 3), catalase. The main role in alcohol metabolism is being payed by cytosolic enzyme, alcohol dehydrogenase, which catalyses metabolism of ethanol to acetaldehyde. It occurs in many dimeric isoenzyme forms which are divided into three classes, according to substrate specifics and other chemical-physical properties. ADH is regulated by development and sex, its activity has been described in many tissues (liver, stomach, kidneys, ovaria, uterus, testes, retina, iris). In 1991 Yoshida found a new gene of alcohol dehydrogenase-ADH 6. 4-hydroxyalkenals, cytotoxic products of lipid peroxidation, are also substrates of ADH. Acetaldehyde is further metabolised by aldehyde dehydrogenase (AIDH) to acetate. AIDH occurs in the form of several isoenzymes in cytosole, mitochondria and microsomes of almost all tissues. Acetaldehyde thus binds to nucleic acids, phospholipids and especially to proteins, it may change their structure and function. In activates collagen synthesis and stimulates lipid peroxidation. Human body may be impaired by immune reaction caused by acetaldehyde binding proteins. Acetaldehyde has the function of a hapten. In 1968 Lieber and DeCarli described microsomal ethanol oxidizing system (MEOS). MEOS is one of cytochrome P450 isoenzymes, now called P450IIE1. Having a gene on chromosome 10, composed of 492 amino acids, this isoenzyme is present in cytoplasmatic reticulum. It is inducible and in case of chronic alcoholism, it accelerates elimination of ethanol from the human body. Inducted P450IIE1 is also present in Kupffer cells which participate in fibrogenesis of liver tissue and produce interleukin 1.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D010089 Oxidoreductases, N-Demethylating N-Demethylase,N-Demethylases,Oxidoreductases, N Demethylating,Demethylating Oxidoreductases, N,N Demethylase,N Demethylases,N Demethylating Oxidoreductases,N-Demethylating Oxidoreductases
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000426 Alcohol Dehydrogenase A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen. Alcohol Dehydrogenase (NAD+),Alcohol Dehydrogenase I,Alcohol Dehydrogenase II,Alcohol-NAD+ Oxidoreductase,Yeast Alcohol Dehydrogenase,Alcohol Dehydrogenase, Yeast,Alcohol NAD+ Oxidoreductase,Dehydrogenase, Alcohol,Dehydrogenase, Yeast Alcohol,Oxidoreductase, Alcohol-NAD+
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000437 Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4) Alcohol Abuse,Alcoholic Intoxication, Chronic,Ethanol Abuse,Alcohol Addiction,Alcohol Dependence,Alcohol Use Disorder,Abuse, Alcohol,Abuse, Ethanol,Addiction, Alcohol,Alcohol Use Disorders,Chronic Alcoholic Intoxication,Dependence, Alcohol,Intoxication, Chronic Alcoholic,Use Disorders, Alcohol
D019392 Cytochrome P-450 CYP2E1 An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse. 4-Nitrophenol-2-Hydroxylase,CYP2E1,Dimethylnitrosamine N-Demethylase,CYP 2E1,CYP IIE1,CYPIIE1,Cytochrome P-450 (ALC),Cytochrome P-450 IIE1,Cytochrome P-450-J,Cytochrome P450 2E1,N-Nitrosodimethylamine Demethylase,4 Nitrophenol 2 Hydroxylase,Cytochrome P 450 CYP2E1,Cytochrome P 450 IIE1,Cytochrome P 450 J,Dimethylnitrosamine N Demethylase,N Nitrosodimethylamine Demethylase

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