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The human cytochrome P450 sub-family: Transcriptional regulation, inter-individual variation and interaction networks

Plant, N (2007) The human cytochrome P450 sub-family: Transcriptional regulation, inter-individual variation and interaction networks BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1770 (3). 478 - 488. ISSN 0304-4165

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Abstract

The Cytochrome P450 super-family is a fundamental requirement for the viability of most life, with Cytochrome P450 proteins having been identified in organisms ranging from bacteria to man. These enzymes may be subdivided into those that metabolise purely endogenous chemicals, and those that are involved in xenobiotic metabolism. Of the latter group it can be argued that CYP3A sub-family members rank as the most important; their high expression in the liver and wide substrate specificity mean that they are clinically important in the metabolism of many therapeutic drugs, and alteration in their activity is central to many clinically-relevant drug–drug interactions. In this review I will examine the human CYP3A enzymes, discussing their genome structure, common allelic variants and, in greatest detail, their transcriptional regulation. Through examination of these characteristics we will see both striking similarities and differences between the four human CYP3A enzymes, which may have important impacts on inter-individual response to chemical exposure. Finally, the role of nuclear receptors in regulating CYP3A gene expression, and indeed that of many other proteins involved in drug metabolism, will be examined: Such an examination will show the need to utilize a systems biology approach to understand fully how the human body responds to chemical exposure.

Item Type: Article
Uncontrolled Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, CYP3A, gene expression, PXR, CAR, nuclear receptor, inter-individual variability, drug-drug interactions, PREGNANE-X-RECEPTOR, ORPHAN NUCLEAR RECEPTOR, DRUG-METABOLIZING-ENZYMES, SITE-DIRECTED MUTAGENESIS, CYP3A4 ACTIVE-SITE, HUMAN LIVER, HUMAN HEPATOCYTES, PHARMACOKINETIC INTERACTIONS, MIDAZOLAM CLEARANCE, GENE-EXPRESSION
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Divisions: Faculty of Health and Medical Sciences > Biochemistry and Physiology
Depositing User: Mr Adam Field
Date Deposited: 27 May 2010 14:46
Last Modified: 23 Sep 2013 18:36
URI: http://epubs.surrey.ac.uk/id/eprint/1948

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