Dalet-Beluche I, Boulenc X, Fabre G, Maurel P, Bonfils C
Institut National de la Santé et de la Recherche Médicale, Unité 128, Montpellier, France.
Eur J Biochem. 1992 Mar 1;204(2):641-8. doi: 10.1111/j.1432-1033.1992.tb16677.x.
Two cytochrome P450 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 P450 MK2 from crab-eating monkeys (Macaca irus) and closely resembles the human P450 3A isozymes. This cytochrome was able to oxidize nifedipine and hydroxylate testosterone at the 6 beta position. The second baboon cytochrome (FI) is closely related to the P450 2A subfamily and has the same N-terminal sequence as human P450 2A7. Like human P450 2A forms, it is highly active as a coumarin 7-hydroxylase. Antibodies against P450 FA and FI cross-react 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.
从苯巴比妥诱导的狒狒（豚尾狒狒）肝脏微粒体中分离并鉴定出两种细胞色素P450同工酶，FA和FI。细胞色素FA具有与食蟹猴（食蟹猕猴）的P450 MK2相同的N端氨基酸序列，并且与人类P450 3A同工酶非常相似。这种细胞色素能够氧化硝苯地平并使睾酮在6β位羟化。第二种狒狒细胞色素（FI）与P450 2A亚家族密切相关，并且与人类P450 2A7具有相同的N端序列。与人类P450 2A形式一样，它作为香豆素7-羟化酶具有高活性。针对P450 FA和FI的抗体分别与两种51 kDa和49 kDa的人类肝脏蛋白发生交叉反应。人类样品中第一种蛋白的浓度比第二种高五倍。然而，后者表现出明显的个体间差异。在人肝细胞原代培养物中，利福平是51 kDa蛋白的强诱导剂，是49 kDa蛋白的中度诱导剂，而苯巴比妥对这两种蛋白有相反的作用。
