The mechanistic plurality of cytochrome P-450 and its biological ramifications

Abstract
The mechanistic plurality of the microsomal cytochrome P-450 enzyme system was illustrated by studies of the oxidative metabolism of benzo[a]pyrene, 3-hydroxybenzo[a]pyrene and arachidonic acid. Rat liver microsomal metabolism of benzo[a]pyrene or 3-hydroxy-benzo[a]pyrene, supported by cumene hydroperoxide, generated benzo[a]pyrene quinones via molecular O-dependent and -independent pathways. Arachidonic acid was metabolized by rat liver microsomal fractions to a variety of oxygenated products, including cis-trans diene conjugated monohydroxy acids, epoxyacids and .omega.- and .omega.-1-oxidation products. The chemistry of the different reaction products is discussed in terms of the possible mechanisms responsible for their formation and the role of the hemoprotein during catalysis. An integrated view for the reaction cycle of cytochrome P-450 was presented.

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