Acetaldehyde generating enzyme systems: Roles of alcohol dehydrogenase, CYP2E1 and catalase, and speculations on the role of other enzymes and processes

Research output: Chapter in Book/Report/Conference proceedingConference contribution

28 Citations (Scopus)

Abstract

Most acetaldehyde is generated in the liver by alcohol dehydrogenase (ADH) during ethanol metabolism. Polymorphic variants of these genes encode enzymes with altered kinetic properties, and pathophysiological effects of these variants may be mediated by accumulation of acetaldehyde. Two additional pathways of acetaldehyde generation are by the cytochrome P450 2E1 (CYP2E1) and catalase. While the amount of ethanol oxidized by these enzymes comprises a small fraction of total body ethanol clearance, the local formation of acetaldehyde by these enzymes may have important effects. Additional sources of acetaldehyde include other minor enzymes (nitric oxide synthase, other cytochrome P450s, P450 reductase, xanthine oxidoreductase) as well as non-enzymatic pathways (formation of hydroxyethyl radicals from the reaction of ethanol with hydroxyl radical, and its subsequent decomposition to acetaldehyde). Acetaldehyde may have effects locally (in the cells generating it), or when delivered to other cells by the blood stream or saliva, or by diffusion from the lumen of the gastrointestinal tract. The ultimate determinants of acetaldehyde toxicity include rates of its formation, rates of oxidation, and the capacity of cellular systems to prevent or repair chemical effects of acetaldehyde (e.g. formation of protein adducts or modification of nucleic acid bases).

Original languageEnglish
Title of host publicationNovartis Foundation Symposium
Pages4-16
Number of pages13
Volume285
StatePublished - 2007

Publication series

NameNovartis Foundation Symposium
Volume285
ISSN (Print)15282511

Fingerprint

Cytochrome P-450 CYP2E1
Acetaldehyde
Alcohol Dehydrogenase
Catalase
Enzymes
Ethanol
Xanthine Dehydrogenase
NADPH-Ferrihemoprotein Reductase
Saliva
Nitric Oxide Synthase
Hydroxyl Radical
Nucleic Acids
Gastrointestinal Tract
Blood Cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Acetaldehyde generating enzyme systems : Roles of alcohol dehydrogenase, CYP2E1 and catalase, and speculations on the role of other enzymes and processes. / Crabb, David; Liangpunsakul, Suthat.

Novartis Foundation Symposium. Vol. 285 2007. p. 4-16 (Novartis Foundation Symposium; Vol. 285).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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AB - Most acetaldehyde is generated in the liver by alcohol dehydrogenase (ADH) during ethanol metabolism. Polymorphic variants of these genes encode enzymes with altered kinetic properties, and pathophysiological effects of these variants may be mediated by accumulation of acetaldehyde. Two additional pathways of acetaldehyde generation are by the cytochrome P450 2E1 (CYP2E1) and catalase. While the amount of ethanol oxidized by these enzymes comprises a small fraction of total body ethanol clearance, the local formation of acetaldehyde by these enzymes may have important effects. Additional sources of acetaldehyde include other minor enzymes (nitric oxide synthase, other cytochrome P450s, P450 reductase, xanthine oxidoreductase) as well as non-enzymatic pathways (formation of hydroxyethyl radicals from the reaction of ethanol with hydroxyl radical, and its subsequent decomposition to acetaldehyde). Acetaldehyde may have effects locally (in the cells generating it), or when delivered to other cells by the blood stream or saliva, or by diffusion from the lumen of the gastrointestinal tract. The ultimate determinants of acetaldehyde toxicity include rates of its formation, rates of oxidation, and the capacity of cellular systems to prevent or repair chemical effects of acetaldehyde (e.g. formation of protein adducts or modification of nucleic acid bases).

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