Bioelectrochemistry of Drug Metabolising Human Flavin- Containing Monooxygenase

The mammalian flavin-containing monooxygenase (FMO) is a widely distributed enzyme that catalyses the NADPH-dependent incorporation of one atom of molecular oxygen into a wide variety of drugs and xenobiotics resulting in more polar metabolites that can be readily excreted [1-2]. They constitute the second most important human monooxygenase system after cytochrome P450s and like the latter, are microsomal Phase I enzymes. Furthermore, many of the cytochrome P450 substrates are also metabolised by FMOs however, the resulting metabolites are distinct. Five different genes encoding for functional forms of human FMO proteins have been identified. One of these expressed genes, FMO3, is the predominant FMO present in adult human liver and exhibits genetic polymorphisms. No direct electrochemical characterisation of FMO proteins has been reported in the literature. The only published data is limited to the measurement of oxygen depletion using a Clark-type electrode [3-4]. Here we report the first direct electrochemistry of human FMO3 immobilised on glassy carbon electrode.