Abstract
The biochemical mechanism for the reduction of misonidazole [1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol] by purified rabbit liver NADPH-cytochrome c (P-450) reductase, the primary nitroreductase of liver, has been studied. Neither the anaerobic nor the futile aerobic reduction velocities exhibited signs of Michaelis-Menten saturation at concentrations less than 5 and 10 mM, respectively. The anaerobic reduction of misonidazole resulted in the formation of glyoxal from fragmentation of the imidazole ring in 25% yield. The rate of glyoxal formation was linear with time and paralleled the reduction of misonidazole, suggesting that it was derived from the partitioning of a reactive intermediate between at least two alternative pathways. Negligible amounts of the 2-amino derivative of misonidazole were formed, however, indicating the existence of alternative reduction/fragmentation pathways.
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