Lipid-protein interactions as determinants of activation or inhibition by cytochrome b5 of cytochrome P-450-mediated oxidations.
Bosterling-B; Trudell-JR; Trevor-AJ; Bendix-M
J Biol Chem 1982 Apr; 257(8):4375-4380
Reconstituted cytochrome-P-450 systems were used to study the effects of cytochrome-b5 on the oxidation of a single substrate, benzphetamine (156081). Cytochrome-P-450 and NADPH-cytochrome-P-450- reductase were derived from livers of rabbits pretreated with phenobarbital. Micelle reconstituted systems and vesicle reconstituted systems were used. Variations in the molar ratio of NADPH-cytochrome-P-450-reductase to cytochrome-b5 to cytochrome-P- 450 and the ratios of proteins to phospholipids resulted in significant changes of metabolic activity. Depending on the system, cytochrome-b5 could be shown to exert no effect on benzphetamine N- demethylation, to cause almost complete inhibition of substrate oxidation, or to cause a three fold higher activity. These results were discussed in terms of a proposed model of lipid protein interactions. In the model, inhibition of cytochrome-P-450 mediated reactions resulted from changes in phospholipid/protein interactions and activation occurred via facilitation of electron transfer between NADPH-cytochrome-P-450-reductase and cytochrome-P-450 in the membrane.
NIOSH-Publication; NIOSH-Grant; Grants-other; Liver-microsomes; Microsomal-enzymes; Enzyme-activity; In-vitro-studies
Anesthesia Stanford University Department of Anesthesia Stanford, Calif 94305
Other Occupational Concerns; Grants-other
Journal of Biological Chemistry
Stanford University, Stanford, California