Oxidative and reductive metabolism by cytochrome P450 2E1

Research output: Contribution to journalArticle

550 Citations (Scopus)

Abstract

We are constantly exposed to many potentially toxic chemicals. Most require metabolic activation to species responsible for cell injury. Although cytochrome P450 2E1 is only one of many different forms of cytochrome P450 that catalyze these reactions, it has an important role in human health as a result of being readily induced by acute and chronic alcohol ingestion. The enzyme efficiently catalyzes the low Km metabolism of compounds commonly used as solvents in industry and at home as well as components found in cigarette smoke, many of which are established carcinogens and hepatotoxins. As a result, there is the potential for increased risk to low level exposure to such chemicals while cytochrome P450 2E1 is induced. Many substrates have been identified for cytochrome P450 2E1. Of the 52 sub-strates for the enzyme identified in this review, the demethylation of N,N-dimethylnitrosamine and the hydroxylation of p-nitrophenol and chlorzoxazone are the most effective for monitoring the level of this enzyme. In addition to oxidative reactions, cytochrome P450 2E1 is also an efficient catalyst of reductive reactions. CCl4-induced hepatotoxicity is one of the best-documented cases for the participation of cytochrome P450 2E1 in a toxicologically important reductive reaction. The reduction of oxygen to superoxide and peroxide are also important reductive reactions of the enzyme and could be important in lipid peroxidation. However, the role of this reaction in vivo remains controversial.

Original languageEnglish (US)
Pages (from-to)724-730
Number of pages7
JournalFASEB Journal
Volume6
Issue number2
StatePublished - Jan 6 1992

Fingerprint

Cytochrome P-450 CYP2E1
cytochrome P-450
Metabolism
metabolism
Enzymes
Chlorzoxazone
Dimethylnitrosamine
enzymes
Hydroxylation
Poisons
hepatotoxins
Peroxides
p-nitrophenol
hepatotoxicity
cigarettes
Smoke
Tobacco Products
Superoxides
Carcinogens
Cytochrome P-450 Enzyme System

Keywords

  • Ethanol-inducible
  • Hepatotoxicity
  • Lipid peroxidation
  • P450 2E1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Oxidative and reductive metabolism by cytochrome P450 2E1. / Koop, Dennis.

In: FASEB Journal, Vol. 6, No. 2, 06.01.1992, p. 724-730.

Research output: Contribution to journalArticle

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