title: The functional effects of physical interactions involving cytochromes P450: putative mechanisms of action and the extent of these effects in biological membranes.
abstract: Cytochromes P450 represent a family of enzymes, which are responsible for the oxidative metabolism of a wide variety of xenobiotics. Although the mammalian P450s require interactions with their redox partners in order to function, more recently, P450 system proteins have been shown to exist as multi-protein complexes that include the formation of P450•P450 complexes. Evidence has shown that the metabolism of some substrates by a given P450 can be influenced by the specific interaction of the enzyme with other forms of P450. Detailed kinetic analysis of these reactions in vitro has shown that the P450-P450 interactions can alter metabolism by changing the ability of a P450 to bind to its cognate redox partner, NADPH-cytochrome P450 reductase; by altering substrate binding to the affected P450; and/or by changing the rate of a catalytic step of the reaction cycle. This review summarizes the known examples of P450-P450 interactions that have been shown in vitro to influence metabolism and categorizes them according to the mechanism(s) causing the effects. P450-P450 interactions have the potential to cause major changes in the metabolism and elimination of drugs in vivo. This review summarizes the evidence that the P450-P450 interactions influence metabolism in biological membranes and discusses the studies, which will provide further insight into the extent of these effects in the future.
authors: a Department of Pharmacology and Experimental Therapeutics, and The Stanley S. Scott Cancer Center , Louisiana State University Health Sciences Center , New Orleans , LA , USA.
authors: James R
authors: JR
authors: Reed
authors: a Department of Pharmacology and Experimental Therapeutics, and The Stanley S. Scott Cancer Center , Louisiana State University Health Sciences Center , New Orleans , LA , USA.
authors: Wayne L
authors: WL
authors: Backes
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046912:Multiprotein Complexes / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase
keywords: Cytochrome P450; drug metabolism; enzyme activation; enzyme inhibition; protein–protein interactions