RT Journal Article
SR Electronic
T1 NADPH–Cytochrome P450 Oxidoreductase: Roles in Physiology, Pharmacology, and Toxicology
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 12
OP 23
DO 10.1124/dmd.112.048991
VO 41
IS 1
A1 David S. Riddick
A1 Xinxin Ding
A1 C. Roland Wolf
A1 Todd D. Porter
A1 Amit V. Pandey
A1 Qing-Yu Zhang
A1 Jun Gu
A1 Robert D. Finn
A1 Sebastien Ronseaux
A1 Lesley A. McLaughlin
A1 Colin J. Henderson
A1 Ling Zou
A1 Christa E. Flück
YR 2013
UL http://dmd.aspetjournals.org/content/41/1/12.abstract
AB 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 b5, 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 b5 are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b5 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.