Soluble nitro reductases

Biorcduction of nitro compounds is carried out by NADPH-dependent microsomal and soluble nitro reductases present in the liver. A multicomponent hepatic microsomal reductase system requiring NADPH appears to be responsible for azo reduction. " " In addition, bacterial reductases present in the intestine can reduce nitro and azo compounds, especially those that are absorbed poorly or excreted mainly in the bile. - ... 

Nitrobenzene reductase activity has been detected in the fat body, gut, and Malpighian tubules of the Madagascar cockroach, G. portentosa (Rose and Young, 1973). Anaerobic conditions are essential for activity. The enzymes in the microsomes are strongly NADH dependent, whereas those in the soluble fraction are strongly NADPH dependent. Activity is enhanced by the addition of flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) or riboflavin. It appears that the true substrate for the nitroreductase is FMN and that the reduction of the nitro compounds occurs nonenzymatically (Figure 8.15). Similar results are obtained using azofuchsin as substrate. 

The enzymes responsible for reduction may be located in both the microsomal fraction and the soluble cell fraction. Reductases in the microflora present in the gastrointestinal tract may also have an important role in the reduction of xenobiotics. There are a number of different reductases which can catalyse the reduction of azo and nitro compounds. Thus, in the microsomal fraction, cytochromes P-450 and possibly a flavoprotein are capable of reductase activity. NADPH is required, but the reaction is inhibited by oxygen. FAD alone may also catalyse reduction by acting as an electron donor. 

B. Reduction The enzymology of reduction is not as well as characterized as for oxidation but, for example, reductive reactions can be catalyzed by cytochrome P-450 and P-450 reductase and soluble enzymes such as DT-diaphorase (EC 1.6.99.2) Many compounds including azo-and nitro-compounds, epoxides, heterocycles and halogenated hydrocarbons Sources of reducing equivalents for the reactions include NAD PH and NADH. Chemical groups modified include nitro, nitroso, tertiary amine oxide, hydroxylamine, azo, quinone, nitroso, alkylhalide... 

By contrast, niridazole and some other nitro compounds are not reduced via cyto chrome P-450 but are reduced by NADPH cytochrome c reductase in hepatic microsomes and xanthine oxidase in the soluble fraction of liver. 

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