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NADPH-cytochrome P450 oxidoreductase: Roles in physiology, pharmacology, and toxicology

Riddick, DS and Ding, X and Wolf, CR and Porter, TD and Pandey, AV and Zhang, Q and Gu, J and Finn, RD and Ronseaux, S and McLaughlin, LA and Henderson, CJ and Zou, L and Fluck, CE (2013) NADPH-cytochrome P450 oxidoreductase: Roles in physiology, pharmacology, and toxicology. Drug Metabolism and Disposition. pp. 12-23.

Abstract

This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH-cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b<sub>5</sub>, squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b <sub>5</sub>are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b<sub>5</sub> on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell-culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism. Copyright 2013 by The American Society for Pharmacology and Experimental Therapeutics

Item Type: Article
Additional Information: pubid: 155 nvp_institute: NIBR contributor_address: (Riddick) Department of Pharmacology and Toxicology, Medical Sciences Building, University of Toronto, Toronto, ON M5S 1A8, Canada (Ding, Zhang, Gu) Wadsworth Center, New York State Department of Health, Albany, NY, United States (Ding, Zhang, Gu) School of Public Health, State University of New York at Albany, Albany, NY, United States (Wolf, Finn, Ronseaux, McLaughlin, Henderson) Molecular Pharmacology Group, Division of Cancer Research, University of Dundee, Dundee, United Kingdom (Wolf, Finn, Ronseaux, McLaughlin, Henderson) Jacqui Wood Cancer Centre, Ninewells Hospital and Medical School, Dundee, United Kingdom (Porter, Zou) Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, United States (Pandey, Fluck) Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, University of Bern, Bern, Switzerland (Ronseaux) Novartis Institutes for BioMedical Research Inc., Cambridge, MA, United States
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/21987

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