Electrocatalytic drug metabolism by CYP2C9 bonded to a self-assembled monolayer-modified electrode. Drug Metab. Dispos

Cytochrome P450 (P450) enzymes typically require the presence of at least cytochrome P450 reductase (CPR) and NADPH to carry out the metabolism of xenobiotics. To address whether the need for redox transfer proteins and the NADPH cofactor protein could be obviated, CYP2C9 was bonded to a gold electrode through an 11-mercaptoundecanoic acid and octanethiol self-assembled mono-layer (SAM) through which a current could be applied. Cyclic voltam-metry demonstrated direct electrochemistry of the CYP2C9 enzyme bonded to the electrode and fast electron transfer between the heme iron and the gold electrode. To determine whether this system could metabolize warfarin analogous to microsomal or expressed enzyme systems containing CYP2C9, warfarin was incubated with the CYP2C9-SAM-gold electrode and a controlled potential was applied. The expected 7-hydroxywarfarin metabolite was observed, analo-gous to expressed CYP2C9 systems, wherein this is the predominan