Abstract
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
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