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Journal ArticleDOI

The human hepatic cytochromes P450 involved in drug metabolism.

TLDR
The purpose of this review is to compare and contrast the human P 450s involved in drug metabolism with their related forms in the rat and other experimental species with respect to their relative levels of the various P450s and their metabolic capabilities.
Abstract
The cytochromes P450 are a superfamily of hemoproteins that catalyze the metabolism of a large number of xenobiotics and endobiotics. The type and amount (i.e., the animal's phenotype) of the P450s expressed by the animal, primarily in the liver, thus determine the metabolic response of the animal to a chemical challenge. A majority of the characterized P450s involved in hepatic drug metabolism have been identified in experimental animals. However, recently at least 12 human drug-metabolizing P450s have been characterized at the molecular and/or enzyme level. The characterization of these P450s has made it possible to "phenotype" microsomal samples with respect to their relative levels of the various P450s and their metabolic capabilities. The purpose of this review is to compare and contrast the human P450s involved in drug metabolism with their related forms in the rat and other experimental species.

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Citations
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Journal ArticleDOI

Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity.

TL;DR: P450s also catalyze less generally discussed reactions including reduction, desaturation, ester cleavage, ring expansion, ring formation, aldehyde scission, dehydration, ipso attack, coupling reactions, rearrangement of fatty acid and prostaglandin hydroperoxides, and phospholipase activity.
Journal ArticleDOI

CYTOCHROME P-450 3A4: Regulation and Role in Drug Metabolism

TL;DR: Several issues remain to be resolved regarding the catalytic activity of the P-450 3A4 protein, including rate-limiting steps and the need for cytochrome b5, divalent cations, and acidic phospholipid systems for optimal activity.
Journal ArticleDOI

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism.

TL;DR: Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates.
Journal Article

Characterization of Interintestinal and Intraintestinal Variations in Human CYP3A-Dependent Metabolism

TL;DR: The results demonstrate that the upper small intestine serves as the major site for intestinal CYP3A-mediated first-pass metabolism and provides a rationale for interindividual differences in oral bioavailability for some CYP 3A substrates.
References
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Journal ArticleDOI

Polymorphic hydroxylation of debrisoquine in man

TL;DR: Family studies supported the view that alicyclic 4-hydroxylation of debrisoquine is controlled by a single autosomal gene and that a defect in this metabolic step is caused by a recessive allele.
Journal ArticleDOI

Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects

TL;DR: The results collectively indicate that P-450 IIE1 is a major catalyst of the oxidation of benzene, styrene, CCl4, CHCl3, CH2Cl2, CH3Cl, 1,2-dichloropropane, ethylene dichloride, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethylcarbamate, and trichloroethylene.
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Purification and characterization of liver microsomal cytochromes p-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone.

TL;DR: The results clearly demonstrate that individual forms of P-450 can be induced by different compounds and that a single compound can lower the level of one form of P -450 while inducing one or more other forms ofP-450.
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