The S-oxidation of thioamides by rat liver microsomes.

In the Vertebrates the two primary catalysts for the oxidation of xenobiotic sulphur-containing compounds appear to be the Flavin-containing monoxygenases. (FMO) and the cytochrome P-450 mooxygenases (P-450) [l]. The relative contribution of these enzyme systems to the oxidation of the vast majority of xenobiotics is unknown [l]. Thioamide compounds, such as thioacetamide, thiobenzamide , ethionamide (ETH,2-ethyl-iso thionicotinamide) thionicotinamide (TNA) are all known to be substrates of the FM0[1,2,3]. However the involvement of the P-450 monooxygenases cannot be ruled out as certain P-450 isoenzymes have been shown to play a role in thioamide S-oxidation [4,5,61. The aim of the current investigation was to determine the contribution of the FMO and P-450 monoxygenases to the microsomal S-oxidation of TNA and ETH. The effects of NADPH, heat and various enzyme inhibitors were used in incubations with microsomes prepared from male Wistar rats [3]. The formation of thioamide S-oxide was determined by HPLC [7] and the results are presented in Table 1. In the absence of an NADPH regenerating system the formation of TNA and ETH S-oxides was significantly reduced. SKF 525A, metyrapone and n-octylamine, known inhibitors of the P-450 monoxygenases [8,9], did not have any significant effect on the S-oxidation of either TNA OK ETH by the liver microsomes, when added at a final concentration of 1mM.