Catalytic activities of human cytochrome P450 2C9*1, 2C9*3 and 2C9*13

Xenobiotica. 2005 Sep;35(9):853-61. doi: 10.1080/00498250500256367.


Cytochrome P450 2C9 (CYP2C9) is a geneticly polymorphic enzyme responsible for the metabolism of some clinically important drugs. CYP2C9*13 is an allele identified in a Chinese poor metabolizer of lornoxicam which has a Leu90Pro amino acid substitution. This paper reports on a study aimed at comparing the catalytic properties of CYP2C9*13 with those of the wild-type CYP2C9*1 and mutant CYP2C9*3 (Ile359Leu) in the COS-7 expression system using various substrates. CYP2C9*3 and *13 produced far lower luminescence than CYP2C9*1 in luciferin H metabolism. CYP2C9*13 exhibited an 11-fold increase in Km but no change in Vmax with tolbutamide as the substrate, a five-fold increase in Km and an 88.8% reduction in Vmax with diclofenac. These data indicate that CYP2C9*13 exhibits reduced metabolic activity toward all studied CYP2C9 substrates. The magnitude of the CYP2C9*13-associated decrease in intrinsic clearance (Vmax/Km) is greater than that associated with CYP2C9*3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Animals
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • Cyclooxygenase Inhibitors / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Cytochrome P-450 CYP2C9
  • Diclofenac / metabolism
  • Diclofenac / pharmacology
  • Humans
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology
  • Kinetics
  • Point Mutation*
  • Substrate Specificity / genetics
  • Tolbutamide / metabolism
  • Tolbutamide / pharmacology


  • Cyclooxygenase Inhibitors
  • Hypoglycemic Agents
  • Diclofenac
  • Tolbutamide
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases