Study of drug metabolism by xanthine oxidase

Int J Mol Sci. 2012;13(4):4873-4879. doi: 10.3390/ijms13044873. Epub 2012 Apr 18.

Abstract

In this work, we report the studies of drug metabolism by xanthine oxidase (XOD) with electrochemical techniques. Firstly, a pair of stable, well-defined and quasi-reversible oxidation/reduction peaks is obtained with the formal potential at -413.1 mV (vs. SCE) after embedding XOD in salmon sperm DNA membrane on the surface of pyrolytic graphite electrode. Then, a new steady peak can be observed at -730 mV (vs. SCE) upon the addition of 6-mercaptopurine (6-MP) to the electrochemical system, indicating the metabolism of 6-MP by XOD. Furthermore, the chronoamperometric response shows that the current of the catalytic peak located at -730 mV increases with addition of 6-MP in a concentration-dependent manner, and the increase of the chronoamperometric current can be inhibited by an XOD inhibitor, quercetin. Therefore, our results prove that XOD/DNA modified electrode can be efficiently used to study the metabolism of 6-MP, which may provide a convenient approach for in vitro studies on enzyme-catalyzed drug metabolism.

Keywords: 6-mercaptopurine; drug metabolism; electrochemistry; quercetin; xanthine oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / metabolism*
  • Catalysis
  • DNA / chemistry
  • Electrochemical Techniques / methods*
  • Electrodes
  • Enzymes, Immobilized / metabolism*
  • Male
  • Mercaptopurine / chemistry
  • Mercaptopurine / metabolism*
  • Oxidation-Reduction
  • Quercetin / pharmacology
  • Salmo salar
  • Spermatozoa / cytology
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / chemistry
  • Xanthine Oxidase / metabolism*

Substances

  • Antimetabolites, Antineoplastic
  • Enzymes, Immobilized
  • DNA
  • Quercetin
  • Mercaptopurine
  • Xanthine Oxidase