CYP2A13-catalysed coumarin metabolism: comparison with CYP2A5 and CYP2A6

Xenobiotica. 2003 Jan;33(1):73-81. doi: 10.1080/0049825021000022302.


1. We investigated the total metabolism of coumarin by baculovirus (BV)-expressed CYP2A13 and compared it with metabolism by BV-expressed CYP2A6. The major coumarin metabolite formed by CYP2A13 was 7-hydroxycoumarin, which accounted for 43% of the total metabolism. The product of 3,4-epoxidation, o-hydroxyphenylacetaldehyde (o-HPA), accounted for 30% of the total metabolites. 2. The K(m) and V(max) for CYP2A13-mediated coumarin 7-hydroxylation were 0.48+/-0.07 micro m and 0.15+/-0.006 nmol min(-1) nmol(-1) CYP, respectively. The V(max) of coumarin 7-hydroxylation by CYP2A13 was about 16-fold lower than that of CYP2A6, whereas the K(m) was 10-fold lower. 3. In the mouse, there were two orthologues for CYP2A6: CYP2A4 and CYP2A5, which differed by only 11 amino acids. However, CYP2A5 is an efficient coumarin 7-hydroxylase, where as CYP2A4 is not. We report here that BV-expressed CYP2A4 metabolizes coumarin by 3,4-epoxidation. Two products of the 3,4-epoxidation pathway, o-HPA and o-hydroxyphenylacetic acid (o-HPAA), were detected by radioflow HPLC. 4. The K(m) and V(max) for the coumarin 3,4-epoxidation by CYP2A4 were 8.7+/-3.6 micro m and 0.20+/-0.04 nmol min(-1) nmol(-1) CYP, respectively. Coumarin 7-hydroxylation by CYP2A5 was more than 200 times more efficient than 3,4 epoxidation by CYP2A4.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticoagulants / metabolism*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Chromatography, High Pressure Liquid
  • Coumarins / metabolism*
  • Cytochrome P-450 CYP2A6
  • Cytochrome P450 Family 2
  • Epoxy Compounds / metabolism
  • Humans
  • Hydroxylation
  • Kinetics
  • Mice
  • Mixed Function Oxygenases / metabolism*
  • Steroid Hydroxylases / metabolism


  • Anticoagulants
  • Coumarins
  • Epoxy Compounds
  • coumarin
  • Mixed Function Oxygenases
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2A13 protein, human
  • CYP2A6 protein, human
  • Cyp2a4 protein, mouse
  • Cyp2a5 protein, mouse
  • Cytochrome P-450 CYP2A6
  • Cytochrome P450 Family 2