Purification of two cytochrome <i>P</i>450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, <i>Papio papio</i>) liver microsomes

Abstract

Two cytochrome P 450 isozymes, FA and FI, were isolated and characterized from liver microsomes of phenobarbital‐induced baboons ( Papio papio ). The cytochrome FA possesses the same N‐terminal amino acid sequence as P 450 MK2 from crab‐eating monkeys ( Macaca irus ) and closely resembles the human P 450 3A isozymes. This cytochrome was able to oxidize nifedipine and hydroxylate testosterone at the 6β position. The second baboon cytochrome (FI) is closely related to the P 450 2A subfamily and has the same N‐terminal sequence as human P 450 2A7. Like human P 450 2A forms, it is highly active as a coumarin 7‐hydroxylase. Antibodies against P 450 FA and FI crossreact with two human liver proteins of 51 kDa and 49 kDa, respectively. The concentration of the first protein in the human samples, was five‐times greater than the second. However, the latter showed marked interindividual variation. In primary cultures of human hepatocytes, rifampicin is a strong inducer of the 51‐kDa protein and a moderate inducer of the 49‐kDa protein, while phenobarbital has the opposite effect on the two proteins.