Metabolism of Alcohol

https://doi.org/10.1016/j.cld.2004.10.005Get rights and content

Section snippets

ADH isozymes

The major pathway for ethanol disposition involves alcohol dehydrogenase (ADH), an enzyme that catalyzes the conversion of ethanol to acetaldehyde. The raison d'être of this enzyme might be to rid the body of the small amounts of alcohol produced by fermentation in the gut [2]. ADH has a broad substrate specificity, which includes dehydrogenation of steroids, oxidation of the intermediary alcohols of the shunt pathway of mevalonate metabolism, and ω-oxidation of fatty acids [3]; these processes

Oxidation of ethanol in the stomach; gender and ethnic differences

Extrahepatic metabolism of ethanol is low, except for the stomach, which is exposed to high ethanol concentrations that can support the activities of enzymes requiring such levels (such as ADH class IV and V). Alcohol was known to disappear from the stomach, and this was considered to be part of its “absorption” from the gastrointestinal tract. It was quantitated postprandially by Cortot et al [207] in seven healthy subjects. They found that of the ingested alcohol, 39.4 ± 4.1% was absorbed

Nonoxidative metabolism of ethanol

Ethanol can form ethyl esters in vivo, and the corresponding enzyme has been purified [266]. Laposata and Lange [267] have found that, compared with controls, in short-term–intoxicated subjects, concentrations of fatty acid ethyl esters were significantly higher in the pancreas, liver, heart, and adipose tissue. Because in humans this nonoxidative ethanol metabolism occurs in the organs most commonly injured by alcohol abuse, and because some of these organs lack oxidative ethanol metabolism,

Summary

Alcohol (ethyl alcohol or ethanol) has been associated with mankind since the dawn of civilization, yet its metabolism has only been elucidated in recent years. It had been known since the beginning of the century that catalase, located in the peroxisomes, can break down ethanol, but it is now realized that except for unusual circumstances, this is a minor pathway. The main pathway proceeds via cytosolic ADH, which has multiple isoenzymes, the genetic polymorphism of which is now being

Acknowledgments

The skillful typing of this manuscript by Ms. Y. Rodriguez and the editorial assistance of F. DeMara are gratefully acknowledged.

First page preview

First page preview
Click to open first page preview

References (269)

  • R. Teschke et al.

    Hepatic microsomal alcohol oxidizing system: solubilization, isolation and characterization

    Arch Biochem Biophys

    (1974)
  • S. Ahmed et al.

    Interactions between alcohol and beta-carotene in patients with alcoholic liver disease

    Am J Clin Nutr

    (1994)
  • K. Ohnishi et al.

    Reconstitution of the microsomal ethanol-oxidizing system: qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption

    J Biol Chem

    (1977)
  • G.T. Miwa et al.

    The direct oxidation of ethanol by catalase- and alcohol dehydrogenase-free reconstituted system containing cytochrome P-450

    Arch Biochem Biophys

    (1978)
  • D.R. Koop et al.

    Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits

    J Biol Chem

    (1982)
  • E.T. Morgan et al.

    Catalytic activity of cytochrome P-450 isozyme 3a isolated from liver microsomes of ethanol-treated rabbits

    J Biol Chem

    (1982)
  • E.T. Morgan et al.

    Comparison of six rabbit liver cytochrome P-450 isozymes in formation of a reactive metabolite of acetaminophen

    Biochem Biophys Res Commun

    (1983)
  • M. Ingelman-Sundberg et al.

    Mechanisms of hydroxyl radical formation and ethanol oxidation by ethanol-inducible and other forms of rabbit liver microsomal cytochromes P-450

    J Biol Chem

    (1984)
  • J.M. Lasker et al.

    Purification and characterization of human liver cytochrome P-450-ALC

    Biochem Biophys Res Commun

    (1987)
  • M. Shimizu et al.

    Immunohistochemical localization of ethanol-inducible P450IIE1 in the rat alimentary tract

    Gastroenterology

    (1990)
  • I. Persson et al.

    Genetic polymorphism of cytochrome P4502E1 in a Swedish population: relation ship to incidence of lung cancer

    FEBS Lett

    (1993)
  • M. Tsutsumi et al.

    Genetic polymorphism of cytochrome P4502E1 related to the development of alcoholic liver disease

    Gastroenterology

    (1994)
  • M.-W. Yu et al.

    Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma

    Gastroenterology

    (1995)
  • J.P. Casazza et al.

    The metabolism of acetone in rat

    J Biol Chem

    (1984)
  • D.R. Koop et al.

    Identification of ethanol-inducible P-450 isozyme 3a as the acetone and acetol monooxygenase of rabbit microsomes

    J Biol Chem

    (1985)
  • J.P. Casazza et al.

    The production of 1,2 propanediol in ethanol treated rats

    Biochem Biophys Res Commun

    (1985)
  • I.J. Johansson et al.

    Hydroxylation of acetone by ethanol- and acetone-inducible cytochrome P450 in liver microsomes and reconstituted membranes

    FEBS Lett

    (1986)
  • L. Chen et al.

    Relationship between cytochrome P450 2E1 and acetone catabolism in rats as studied with diallyl sulfide as an inhibitor

    Biochem Pharmacol

    (1994)
  • R.M. Laethem et al.

    Formation of 19(S)-, 19(R)- and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P4502E1

    J Biol Chem

    (1993)
  • Y. Amet et al.

    Evidence that cytochrome P450 2E1 is involved in the (ω-1)-hydroxylation of lauric acid in rat liver microsomes

    Biochem Biophys Res Commun

    (1994)
  • F. Adas et al.

    Involvement of cytochrome P450 2E1 in the (omega-1)-hydroxylation of oleic acid in human and rat liver microsomes

    J Lipid Res

    (1998)
  • I. Dupont et al.

    Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics

    J Hepatol

    (1998)
  • M.K. Aleynik et al.

    Dilinoleoylphophatidylcholine decreases ethanol-induced cytochrome P4502E1

    Biochem Biophys Res Commun

    (2001)
  • C.S. Lieber et al.

    Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon

    Gastroenterology

    (1994)
  • J.J. Shelmet et al.

    Ethanol causes acute inhibition of carbohydrate, fat, and protein oxidation and insulin resistance

    J Clin Invest

    (1988)
  • I. Bjorkhem

    On the role of alcohol dehydrogenase in ω-oxidation of fatty acids

    Eur J Biochem

    (1972)
  • W.F. Bosron et al.

    Genetic factors in alcohol metabolism and alcoholism

    Semin Liver Dis

    (1993)
  • S.-J. Yin et al.

    Identification of a human stomach alcohol dehydrogenase with distinctive kinetic properties

    Biochem Int

    (1990)
  • M. Yasunami et al.

    A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme

    Proc Natl Acad Sci USA

    (1991)
  • C.S. Lieber et al.

    The effect of ethanol on fatty acid metabolism: stimulation of hepatic fatty acid synthesis in vitro

    J Clin Invest

    (1961)
  • C.S. Lieber

    Metabolism of ethanol

  • J. Faller et al.

    Evidence for increased urate production by activation of adenine nucleotide turnover

    N Engl J Med

    (1982)
  • A. Chedid et al.

    Prognostic factors in alcoholic liver disease

    Am J Gastroenterol

    (1991)
  • B.P. Lane et al.

    Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets

    Am J Pathol

    (1966)
  • B.H. Lauterburg et al.

    Mitochondrial dysfunction in alcoholic patients as assessed by breath analysis

    Hepatology

    (1993)
  • N. Grunnet et al.

    Effect of ethanol on lipid metabolism in cultured hepatocytes

    Biochem J

    (1985)
  • Y. Israel et al.

    Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil

    Proc Natl Acad Sci USA

    (1975)
  • B.J. Kessler et al.

    The hepatic blood flow and splanchnic oxygen consumption in alcohol fatty liver

    J Clin Invest

    (1954)
  • P. Jauhonen et al.

    Mechanism for selective perivenular hepatotoxicity of ethanol

    Alcohol Clin Exp Res

    (1982)
  • C.S. Lieber et al.

    Impaired oxygen utilization: a new mechanism for the hepatotoxicity of ethanol in sub-human primates

    J Clin Invest

    (1989)
  • Cited by (209)

    View all citing articles on Scopus

    Portions of this article appeared previously in Lieber C. Metabolism of alcohol. Clinics in Liver Disease 1998;2(4):673–702; with permission.

    View full text