Induction of drug-metabolizing enzymes: Mechanisms and consequences

Allan B. Okey, Eve A. Roberts, Patricia A. Harper, Michael S. Denison

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

The activity of many enzymes that carry out biotransformation of drugs and environmental chemicals can be substantially increased by prior exposure of humans or animals to a wide variety of foreign chemicals. Increased enzyme activity is due to true enzyme induction mediated by increased synthesis of mRNAs which code for specific drug-metabolizing enzymes. Several species of cytochrome P-450 are inducible as are certain conjugating enzymes such as glutathione S-transferases, glucuronosyl transferases, and epoxide hydrolases. Induction of drug-metabolizing enzymes has been shown in several instances to alter the efficacy of some therapeutic agents. Induction of various species of cytochrome P-450 also is known to increase the rate at which potentially toxic reactive metabolic intermediates are formed from drugs or environmental chemicals. Overall, however, induction of drug-metabolizing enzymes appears to be a beneficial adaptive response for organisms living in a "chemically-hostile" world.

Original languageEnglish (US)
Pages (from-to)132-141
Number of pages10
JournalClinical Biochemistry
Volume19
Issue number2
DOIs
StatePublished - 1986
Externally publishedYes

Keywords

  • biotransformation
  • carcinogenesis
  • cytochrome P-450
  • environmental exposure
  • enzyme induction
  • metabolic detoxication drug
  • polycyclic hydrocarbons
  • receptor drug

ASJC Scopus subject areas

  • Clinical Biochemistry

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    Okey, A. B., Roberts, E. A., Harper, P. A., & Denison, M. S. (1986). Induction of drug-metabolizing enzymes: Mechanisms and consequences. Clinical Biochemistry, 19(2), 132-141. https://doi.org/10.1016/S0009-9120(86)80060-1