A novel CYP2A26 identified in cynomolgus monkey liver metabolizes coumarin

Xenobiotica. 2010 Sep;40(9):621-9. doi: 10.3109/00498254.2010.501118.


A novel cytochrome P450 (CYP), CYP2A26, was identified and characterized in cynomolgus monkey, one of the animal species used in preclinical studies. Deduced amino acid sequences of CYP2A26 cDNA showed high sequence identities (91–95%) with cynomolgus monkey CYP2A23 and CYP2A24, and human CYP2A6 and CYP2A13. Phylogenetic analysis showed that macaque CYP2As (CYP2A26, CYP2A23, and CYP2A24) were most closely clustered with human CYP2As, unlike CYP2As of dog, rat, and mouse (other species also used in drug metabolism). Quantitative polymerase chain reaction analysis showed that CYP2A26 mRNA, along with CYP2A23 and CYP2A24 mRNAs, was expressed predominantly in the liver, where CYP2A proteins were also detected by immunoblotting. Drug-metabolizing assays using the CYP2A26 protein heterologously expressed in Escherichia coli indicated that CYP2A26 catalyzed coumarin 7-hydroxylation with its apparent K(m) lower than that of CYP2A24, but similar to those of CYP2A6 and CYP2A23. These results suggest an evolutionary closeness and functional similarity of cynomolgus monkey CYP2A26 (together with CYP2A23 and CYP2A24) to human CYP2A6, and its functional role as a drug-metabolizing enzyme in the liver.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Coumarins / metabolism*
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Dogs
  • Exons / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Introns / genetics
  • Liver / enzymology*
  • Macaca fascicularis / metabolism*
  • Male
  • Mice
  • Molecular Sequence Data
  • Phylogeny
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Sequence Alignment
  • Sequence Analysis, DNA


  • Coumarins
  • DNA, Complementary
  • RNA, Messenger
  • Cytochrome P-450 Enzyme System

Associated data

  • GENBANK/GU289744