Metabolism of Alcohol
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.
References (269)
- et al.
Role of intestinal bacterial overgrowth in ethanol production and metabolism in rats
Gastroenterology
(1986) - et al.
New human liver alcohol dehydrogenase forms with unique kinetic characteristics
Biochem Biophys Res Commun
(1981) - et al.
Purification and characterization of a new alcohol dehydrogenase from human stomach
J Biochem
(1991) - et al.
Effects of ethanol on fatty acid metabolism in liver slices
Biochem Biophys Res Commun
(1959) - et al.
Effect of acute and chronic ethanol consumption on hepatic tissue oxygen tension in rats
Pharmacol Biochem Behav
(1983) - et al.
Increased hepatic production of alpha-amino-n-butyric acid after chronic alcohol consumption in rats and baboons
Gastroenterology
(1980) - et al.
Role of xanthine oxidase in ethanol-induced lipid peroxidation in rats
Gastroenterology
(1990) - et al.
Hepatic microsomal ethanol oxidizing system: in vitro characteristics and adaptive properties in vivo
J Biol Chem
(1970) - et al.
Characteristics of alcohol dehydrogenase in fat-storing (Ito) cells of rat liver
Gastroenterology
(1988) - et al.
Human hepatic stellate cells express class I alcohol dehydrogenase and aldehyde dehydrogenase but not cytochrome P4502E1
J Hepatol
(1998)
Hepatic microsomal alcohol oxidizing system: solubilization, isolation and characterization
Arch Biochem Biophys
Interactions between alcohol and beta-carotene in patients with alcoholic liver disease
Am J Clin Nutr
Reconstitution of the microsomal ethanol-oxidizing system: qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption
J Biol Chem
The direct oxidation of ethanol by catalase- and alcohol dehydrogenase-free reconstituted system containing cytochrome P-450
Arch Biochem Biophys
Purification and characterization of a unique isozyme of cytochrome P-450 from liver microsomes of ethanol-treated rabbits
J Biol Chem
Catalytic activity of cytochrome P-450 isozyme 3a isolated from liver microsomes of ethanol-treated rabbits
J Biol Chem
Comparison of six rabbit liver cytochrome P-450 isozymes in formation of a reactive metabolite of acetaminophen
Biochem Biophys Res Commun
Mechanisms of hydroxyl radical formation and ethanol oxidation by ethanol-inducible and other forms of rabbit liver microsomal cytochromes P-450
J Biol Chem
Purification and characterization of human liver cytochrome P-450-ALC
Biochem Biophys Res Commun
Immunohistochemical localization of ethanol-inducible P450IIE1 in the rat alimentary tract
Gastroenterology
Genetic polymorphism of cytochrome P4502E1 in a Swedish population: relation ship to incidence of lung cancer
FEBS Lett
Genetic polymorphism of cytochrome P4502E1 related to the development of alcoholic liver disease
Gastroenterology
Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma
Gastroenterology
The metabolism of acetone in rat
J Biol Chem
Identification of ethanol-inducible P-450 isozyme 3a as the acetone and acetol monooxygenase of rabbit microsomes
J Biol Chem
The production of 1,2 propanediol in ethanol treated rats
Biochem Biophys Res Commun
Hydroxylation of acetone by ethanol- and acetone-inducible cytochrome P450 in liver microsomes and reconstituted membranes
FEBS Lett
Relationship between cytochrome P450 2E1 and acetone catabolism in rats as studied with diallyl sulfide as an inhibitor
Biochem Pharmacol
Formation of 19(S)-, 19(R)- and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P4502E1
J Biol Chem
Evidence that cytochrome P450 2E1 is involved in the (ω-1)-hydroxylation of lauric acid in rat liver microsomes
Biochem Biophys Res Commun
Involvement of cytochrome P450 2E1 in the (omega-1)-hydroxylation of oleic acid in human and rat liver microsomes
J Lipid Res
Cytochrome P4502E1 inducibility and hydroxyethyl radical formation among alcoholics
J Hepatol
Dilinoleoylphophatidylcholine decreases ethanol-induced cytochrome P4502E1
Biochem Biophys Res Commun
Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon
Gastroenterology
Ethanol causes acute inhibition of carbohydrate, fat, and protein oxidation and insulin resistance
J Clin Invest
On the role of alcohol dehydrogenase in ω-oxidation of fatty acids
Eur J Biochem
Genetic factors in alcohol metabolism and alcoholism
Semin Liver Dis
Identification of a human stomach alcohol dehydrogenase with distinctive kinetic properties
Biochem Int
A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme
Proc Natl Acad Sci USA
The effect of ethanol on fatty acid metabolism: stimulation of hepatic fatty acid synthesis in vitro
J Clin Invest
Metabolism of ethanol
Evidence for increased urate production by activation of adenine nucleotide turnover
N Engl J Med
Prognostic factors in alcoholic liver disease
Am J Gastroenterol
Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets
Am J Pathol
Mitochondrial dysfunction in alcoholic patients as assessed by breath analysis
Hepatology
Effect of ethanol on lipid metabolism in cultured hepatocytes
Biochem J
Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil
Proc Natl Acad Sci USA
The hepatic blood flow and splanchnic oxygen consumption in alcohol fatty liver
J Clin Invest
Mechanism for selective perivenular hepatotoxicity of ethanol
Alcohol Clin Exp Res
Impaired oxygen utilization: a new mechanism for the hepatotoxicity of ethanol in sub-human primates
J Clin Invest
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Portions of this article appeared previously in Lieber C. Metabolism of alcohol. Clinics in Liver Disease 1998;2(4):673–702; with permission.