Abstract

We propose that the cytochrome P-450 mixed function oxidase reaction contains two reactions, one an NADPH oxidase and the other a monooxygenase reaction. To date attempts to study stoichiometries of the monooxygenase reaction have been confused by the generation of H2O2, a component of the NADPH-oxidase. We have developed a mechanism which envelopes both reactions and will attempt to show that during the mixed function oxidase reaction, uncoupling of active oxygen with subsequent discharge of oxygenated cytochrome P-450, yields H2O2. Influence of different substrates on the stoichiometries will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026548-07
Application #
3273994
Study Section
Toxicology Study Section (TOX)
Project Start
1978-08-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Connecticut
Department
Type
School of Medicine & Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code

  Publications

Jansson, I; Mole, J E; Schenkman, J B (1995) The isolation and comparison of multiple forms of CYP2B from untreated and phenobarbital-treated rabbit liver microsomes. Arch Biochem Biophys 316:275-84
Yonaha, M; Tampo, Y; Clarke, W et al. (1992) Cholate solubilization of liver microsomal membrane components which promote NADPH-supported lipid peroxidation. Arch Biochem Biophys 292:62-9
Davis, H W; Suzuki, T; Schenkman, J B (1987) Oxidation of esterified arachidonate by rat liver microsomes. Arch Biochem Biophys 252:218-28
Jansson, I; Schenkman, J B (1987) Influence of cytochrome b5 on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P-450. Drug Metab Dispos 15:344-8
Tamburini, P P; Schenkman, J B (1987) Purification to homogeneity and enzymological characterization of a functional covalent complex composed of cytochromes P-450 isozyme 2 and b5 from rabbit liver. Proc Natl Acad Sci U S A 84:11-5
Tamburini, P P; Schenkman, J B (1986) Differences in the mechanism of functional interaction between NADPH-cytochrome P-450 reductase and its redox partners. Mol Pharmacol 30:178-85
Tamburini, P P; Schenkman, J B (1986) Mechanism of interaction between cytochromes P-450 RLM5 and b5: evidence for an electrostatic mechanism involving cytochrome b5 heme propionate groups. Arch Biochem Biophys 245:512-22
Tamburini, P P; MacFarquhar, S; Schenkman, J B (1986) Evidence of binary complex formations between cytochrome P-450, cytochrome b5, and NADPH-cytochrome P-450 reductase of hepatic microsomes. Biochem Biophys Res Commun 134:519-26
Tamburini, P P; White, R E; Schenkman, J B (1985) Chemical characterization of protein-protein interactions between cytochrome P-450 and cytochrome b5. J Biol Chem 260:4007-15
Jansson, I; Tamburini, P P; Favreau, L V et al. (1985) The interaction of cytochrome b5 with four cytochrome P-450 enzymes from the untreated rat. Drug Metab Dispos 13:453-8