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Multiple forms of inducible drug-metabolizing enzymes: A reasonable mechanism by which any organism can cope with adversity

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Summary

All organisms possess a number of genetically regulated mechanisms in order to cope with rapid adverse changes in the environment. The two systems which appear to respond to a seemingly endless array of chemical specificities are the immune response and the induction of drug-metabolizing enzymes. Similarities and differences between the immunoglobulin and the cytochrome P-450-mediated monooxygenase systems are described. DNA insertion sequences, plasmid “transposons,” maize “controlling elements,” gene duplication, intervening sequences, and high-frequency intergenic recombination are all discussed as possible methods by which organisms can “adapt” quickly to a new selective pressure. If the regulation of P-450 induction resembles in any way the other methods by which pro- and eukaryotes cope genetically with numerous forms of environmental adversity, therefore, it is very likely that mammalian tissues contain hundreds, if not thousands, of inducible forms of P-450.

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  1. Developmental Pharmacology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 20205, Bethesda, Maryland, USA

    Daniel W. Nebert

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Portions of this overview were presented at the Symposium on “The Effects of Drugs on Enzyme Induction Related to the Metabolism of Drugs and Carcinogenic Compounds,” 14th Symposium Medicum Hoechst, County Mayo, Ireland, May, 1978 (1), and the Symposium on “Isolated Drug-Metabolizing Enzymes,” Mainz, Germany, July, 1978 (2). The author is Chief of the Developmental Pharmacology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20205.

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Nebert, D.W. Multiple forms of inducible drug-metabolizing enzymes: A reasonable mechanism by which any organism can cope with adversity. Mol Cell Biochem 27, 27–46 (1979). https://doi.org/10.1007/BF00849277

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