title: NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
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(5), 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(5) are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b(5) 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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8. david.riddick@utoronto.ca
authors.forename: David S
authors.initials: DS
authors.lastname: Riddick
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ding
authors.forename: C Roland
authors.initials: CR
authors.lastname: Wolf
authors.forename: Todd D
authors.initials: TD
authors.lastname: Porter
authors.forename: Amit V
authors.initials: AV
authors.lastname: Pandey
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Finn
authors.forename: Sebastien
authors.initials: S
authors.lastname: Ronseaux
authors.forename: Lesley A
authors.initials: LA
authors.lastname: McLaughlin
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Henderson
authors.forename: Ling
authors.initials: L
authors.lastname: Zou
authors.forename: Christa E
authors.initials: CE
authors.lastname: Flück
mesh_terms: D000483:Alleles; D000818:Animals; D015786:Cytochromes b5 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004364:Pharmaceutical Preparations; D015786:Cytochromes b5; D009251:NADPH-Ferrihemoprotein Reductase