Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes. Cross reactivity with human forms.
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.
Dalet-Beluche
I
I
Institut National de la Santé et de la Recherche Médicale, Unité 128, Montpellier, France.
Boulenc
X
X
Fabre
G
G
Maurel
P
P
Bonfils
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015153:Blotting, Western; D003429:Cross Reactions; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D010215:Papio; D010634:Phenobarbital / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D013739:Testosterone / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D007527:Isoenzymes; D015262:Xenobiotics; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; D065637:Cytochrome P-450 CYP2A6; D051544:Cytochrome P-450 CYP3A; D010634:Phenobarbital