Detoxification pathways in the liver
- 1 July 1991
- journal article
- review article
- Published by Wiley in Journal of Inherited Metabolic Disease
- Vol. 14 (4), 421-430
- https://doi.org/10.1007/bf01797915
Abstract
The liver plays an important rôle in protecting the organism from potentially toxic chemical insults through its capacity to convert lipophiles into more water-soluble metabolites which can be efficiently eliminated from the body via the urine. This protective ability of the liver stems from the expression of a wide variety of xenobiotic biotransforming enzymes whose common underlying feature is their ability to catalyse the oxidation, reduction and hydrolysis (Phase I) and/or conjugation (Phase II) of functional groups on drug and chemical molecules. The broad substrate specificity, isoenzyme multiplicity and inducibility of many of these enzyme systems make them particularly well adapted to handling the vast array of different chemical structures in the environment to which we are exposed daily. However, some chemicals may also be converted to more toxic metabolites by certain of these enzymes, implying that variations in the latter may be important predisposing factors for toxicity. Pharmacogenetic defects of xenobiotic biotransformation enzymes, a subclass of inborn errors of metabolism which are manifested only upon drug challenge, introduce marked variation into human populations for the pharmacokinetics and pharmacodynamics of therapeutic and toxic agents, and thus may have important clinical consequences for drug efficacy and toxicity.This publication has 17 references indexed in Scilit:
- Enzyme induction in the cytochrome P-450 systemPharmacology & Therapeutics, 1990
- Molecular genetics and the future of pharmacogeneticsPharmacology & Therapeutics, 1990
- Human ArylamineN-Acetyltransferase Genes: Isolation, Chromosomal Localization, and Functional ExpressionDNA and Cell Biology, 1990
- Acetylation pharmacogenetics. The slow acetylator phenotype is caused by decreased or absent arylamine N-acetyltransferase in human liver.JCI Insight, 1990
- Genetic Polymorphisms of Drug MetabolismAdvances in Drug Research, 1990
- N-acetyltransferasePharmacology & Therapeutics, 1989
- Evidence for two closely related isozymes of arylamine N‐acetyltransferase in human liverFEBS Letters, 1989
- Evolution of the cytochrome P450 genesXenobiotica, 1989
- A simple test for acetylator phenotype using caffeine.British Journal of Clinical Pharmacology, 1984
- Products of Metabolism of CaffeinePublished by Springer Science and Business Media LLC ,1984