RT Journal Article
SR Electronic
T1 THE ROLE OF OXYGENATED CYTOCHROME P-450 AND
OF CYTOCHROME <em>b</em><sub>5</sub> IN HEPATIC MICROSOMAL
DRUG OXIDATIONS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 129
OP 138
VO 1
IS 1
A1 JEFFREY BARON
A1 ALFRED G. HILDEBRANDT
A1 JULIAN A. PETERSON
A1 RONALD W. ESTABROOK
YR 1973
UL http://dmd.aspetjournals.org/content/1/1/129.abstract
AB An examination of the spectral changes occurring in hepatic microsomes during the aerobic steady state of oxidative drug metabolism has revealed the presence of a spectral species which has been identified as the oxygenated form of ferrous cytochrome P-450. The appearance of this species in hepatic microsomes depends on 1) the presence of a type I substrate which can undergo oxidation, 2) the presence of oxygen, and 3) the use of TPNH as the source of reducing equivalents. The rate of formation of this oxygenated form of cytochrome P-450 is much faster that the overall rate of substrate oxidation and is consistent with the inclusion of this intermediate in the sequence of cyclic reduction and oxidation transitions which cytochrome P-450 undergoes during substrate oxidation. The observation that the presence of drug substrates produces a partial reoxidation of TPNH-reduced cytochrome b5, thereby resulting in a lower aerobic steady-state level of reduction of this hemoprotein, indicates that cytochrome b5 may function in hepatic microsomal drug oxidations. It is proposed that reduced cytochrome b5 may serve in the capacity of an electron transfer intermediate which donates the electron to oxygenated cytochrome P-450 required for substrate oxidation. Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics