독성학과 약물치료에서 FMO의 역할에 관한 연구

초록

Among many hepatic microsomal enzymes involved in drug metabolism, the flavin-containing monooxygenase (FMO) are known to be present at high concentrations together with the heme (cytochrome P-450)-containing mixed function oxidases(MFO) and both together are known to play crucial role in the initial oxidation of manu clinical medicines and dietary plant alkaloids. Both the MFO and FMO use NADPH and oxygen as respective sources of electron input and oxygenation for eventual oxidation of lipid soluble drugs to make then more polar and easily excreted. However, unlike the MFO which is kept under inactive state and requires activation by the binding of acidic substrates at neutral pH, the FMO is kept under reactive state having the 4a-hudroperoxy flavin form to oxidize the basic substrates with high pKa immediately upon contact at basic pH. The hydroperoxy flavin contained in FMO is known to make an electrophilic attack on soft nucleophiles (electron rich atoms) like nitrogen, sulfur and phosphorus contained in medicines and alkaloids. Frequently, MFO and FMO share common substrates but produce different metabolites (1)