Functional Aspects of Protein-Protein Interactions of Cytochrome P450 Cytochrome b5 and Cytochrome P450 Reductase
While cytochrome P450 has only been known for a relatively short time (1), and its role in xenobiotic metabolism has been known for an even shorter period (2), cytochrome b5 has been known for a much longer time (see review, 3). Both of these hemoproteins are present in the endoplasmic reticulum of a number of tissue, particularly the liver. Only in the last two decades has cytochrome b5 been found to play a role in liver microsomal monooxygenations (4–6). The original report of cytochrome b5 involvement in P450 monooxygenations (7) was an attempt to explain NADH synergism of NADPH-supported drug oxidations (8). Subsequent studies including those discussed in this lecture, have resulted in implication of cytochrome b5 in P450 monooxygenations, but do not explain the earlier reported NADH-synergism.
KeywordsP450 Reductase Cytochrome P450 Reductase Redox Partner Charge Pairing Spin Equilibrium
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- 9.J.B. Schenkman, S.G. Sligar and D.L. Cinti, Substrate interaction with cytochrome P-450, p. 587 in “Hepatic Cytochrome P-450 Monooxygenase System”, J.B. Schenkman and D. Kupfer, eds., Pergamon Press, New York (1982).Google Scholar
- 14.J.B. Schenkman, H. Remmer and R.W. Estabrook, Spectral studies of drug interaction with hepatic cytochrome, Mol. Pharmacol. 3:113 (1967).Google Scholar
- 17.P. Strittmatter and H.A. Dailey, Essential features and orientation of cytochrome b5 in membranes, p. 71, in “Membranes and Transport”, Vol. 1, A.N. Martonosi, ed., Plenum Publishing Corporation (1982).Google Scholar
- 23.T.L. Poulos, B.C. Finzel, I.C. Gunsalus, G.C. Wagner and J. Kraut, The 2.6A crystal structure of Pseudomonas putida cytochrome P-450, J. Biol. Chem. 260:122 (1985).Google Scholar
- 29.W.L. Backes and C.E. Reker-Backes, The effect of NADPH concentration on the reduction of cytochrome P-450 LM2, J. Biol. Chem. 263:242 (1988).Google Scholar