Study of Drug Metabolism by Xanthine Oxidase

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.

Anti-Hyperuricemic Effects of Astaxanthin by Regulating Xanthine Oxidase, Adenosine Deaminase and Urate Transporters in Rats

“…The trends of the enzymatic activities of XOD and ADA in the serum were remarkably similar to that of the liver (Figure 2). Many studies have reported that the suppression of the enzymatic activities of XOD and ADA can decrease the synthesis of UA to a greater extent [21,39]. He et al found that the inhibition of the activity of XOD significantly decreased the serum UA level, thereby improving the hyperuricemic condition [40].…”

Mimicking of Phase I Metabolism Reactions of Molindone by HLM and Photocatalytic Methods with the Use of UHPLC-MS/MS

“…The synthesis and isolation of metabolites is a distinct issue. Since the conventional approach of obtaining metabolites assumes organic synthesis, some modern techniques such as biosynthesis, enzymatic methods, and electrochemical (EC) synthetic reactions are particularly gaining attention [35][36][37][38][39][40]. In this context, the photocatalytic transformation of drugs in order to further metabolite isolation seems to become a promising tool.…”