Characterization of a mitochondrial NADH-dependent nitro reductase from rat brain.
Rat brain mitochondria contain an NADH-linked nitro reductase that converts various aromatic nitro compounds, including the anti-schistosomal agent niridazole, into the hydroxylamine metabolites. The enzyme is tightly bound to the inner membrane and its activity is measurable only after disrupting the mitochondria. Triton X-100 (1%) and sonication partially solubilize the enzyme. The molecular weight determined by gel filtration is approx. 200 000. The temperature optima for the membrane-bound and for the solubilized enzyme are at 35 and 30 degrees C, respectively. The pH optimum for the membrane-bound enzyme is 9.2. NAD+ and 4-hydroxymercuribenzoate decrease the enzyme activity. Oxygen, carbon monoxide, cyanide, rotenone, barbiturates, chlorpromazine, dicumarol and chelating agents have no effect on the activity. The subcellular localization, substrate specificity and sensitivity to inhibitors distinguish the mitochondrial nitro reductase from the corresponding microsomal and cytosolic enzymes.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008928:Mitochondria / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology; D009574:Nitro Compounds; D009601:Nitroreductases; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D013367:Submitochondrial Particles / Q000201:enzymology; D013379:Substrate Specificity; D013696:Temperature
D009574:Nitro Compounds; D009243:NAD; D010088:Oxidoreductases; C029492:aromatic NADH-dependent nitroreductase; D009601:Nitroreductases