Induction of drug-metabolizing enzymes: mechanisms and consequences.
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.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D064420:Drug-Related Side Effects and Adverse Reactions; D004785:Environmental Pollutants / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008658:Inactivation, Metabolic; D008748:Methylcholanthrene / Q000494:pharmacology; D009369:Neoplasms / Q000139:chemically induced; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology
D002273:Carcinogens; D004785:Environmental Pollutants; D004364:Pharmaceutical Preparations; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D010634:Phenobarbital