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

Eur J Biochem. 1992 Mar 1;204(2):641-8. doi: 10.1111/j.1432-1033.1992.tb16677.x.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Blotting, Western
  • Cross Reactions
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / isolation & purification*
  • Cytochrome P-450 Enzyme System / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Induction
  • Humans
  • Hydroxylation
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Isoenzymes / isolation & purification*
  • Isoenzymes / metabolism
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Mixed Function Oxygenases / metabolism
  • Molecular Sequence Data
  • Multigene Family*
  • Papio
  • Phenobarbital / pharmacology
  • Sequence Homology, Nucleic Acid
  • Testosterone / metabolism
  • Xenobiotics / metabolism

Substances

  • Isoenzymes
  • Xenobiotics
  • Testosterone
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 CYP3A
  • Phenobarbital