Alcohol metabolism and toxicity

Role of cytochrome P-450

Minor J. Coon, Dennis Koop, Lorraine E. Reeve, Becky L. Crump

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

A new isozyme of cytochrome P-450, designated form 3a on the basis of its relative electrophoretic mobility, has been purified to homogeneity from liver microsomes of rabbits treated chronically with ethanol. This cytochrome has the highest activity of the known rabbit P-450 isozymes in the oxidation of ethanol to acetaldehyde. In view of the reports of others that the hepatotoxicity of acetaminophen is increased in ethanol-treated animals and the human alcoholic, we have determined the activity of the six available P-450 isozymes in the activation of the drug to give an intermediate which forms a conjugate with reduced glutathione. Isozymes 3a, 4, and 6, the three major forms of cytochrome P-450 present in liver microsomes from rabbits chronically treated with ethanol, exhibited the highest activities in the recostituted enzyme system, whereas isozymes 3b and 3c were 10- to 20-fold less effective and phenobarbital-inducible isozyme 2 was essentially inactive, even in the presence of cytochrome b5. The results obtained thus indicate that induction by ethanol of P-450 isozyme 3a may contribute to the toxicity of acetaminophen but that other cytochromes also play a significant role.

Original languageEnglish (US)
Pages (from-to)134-143
Number of pages10
JournalFundamental and Applied Toxicology
Volume4
Issue number2 PART 1
DOIs
StatePublished - 1984
Externally publishedYes

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Metabolism
Cytochrome P-450 Enzyme System
Isoenzymes
Toxicity
Alcohols
Ethanol
Liver Microsomes
Cytochromes
Acetaminophen
Rabbits
Liver
Cytochromes b5
Electrophoretic mobility
Acetaldehyde
Phenobarbital
Glutathione
Animals
Chemical activation
Oxidation
Enzymes

ASJC Scopus subject areas

  • Toxicology

Cite this

Alcohol metabolism and toxicity : Role of cytochrome P-450. / Coon, Minor J.; Koop, Dennis; Reeve, Lorraine E.; Crump, Becky L.

In: Fundamental and Applied Toxicology, Vol. 4, No. 2 PART 1, 1984, p. 134-143.

Research output: Contribution to journalArticle

Coon, Minor J. ; Koop, Dennis ; Reeve, Lorraine E. ; Crump, Becky L. / Alcohol metabolism and toxicity : Role of cytochrome P-450. In: Fundamental and Applied Toxicology. 1984 ; Vol. 4, No. 2 PART 1. pp. 134-143.
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