TY - JOUR T1 - Studies on the Mechanism of Nitro Reduction by Rat Liver JF - Molecular Pharmacology JO - Mol Pharmacol SP - 487 LP - 498 VL - 5 IS - 5 AU - RYUICHI KATO AU - TAKAO OSHIMA AU - AKIRA TAKANAKA Y1 - 1969/09/01 UR - http://molpharm.aspetjournals.org/content/5/5/487.abstract N2 - The reduction of p-nitrobenzoic acid by rat liver was studied by measurement of the disappearance of p-nitrobenzoic acid and the formation of p-hydroxyaminobenzoic acid and of p-aminobenzoic acid. The mechanisms by which flavin mononucleotide stimulates, oxygen inhibits, and phenobarbital and methylcholanthrene induce this enzyme system were particularly investigated. The NADPH-linked and NADH-linked reductases of p-nitrobenzoic acid were assumed to be separate enzymes because of differences in their intracellular localization. The rate of the NADH-linked reduction of p-nitrobenzoic acid of p-hydroxyaminobenzoic acid is neglible in microsomes whereas the rate of the NADPH-linked reduction of p-nitrobenzoic acid to p-hydroxyaminobenzoic acid is comparable to that of the reduction of p-hydroxyaminobenzoic acid to p-aminobenzoic acid. The reduction of p-nitrobenzoic acid to p-hydroxyaminobenzoic acid is stimulated by flavin mononucleotide, and the reduced compound accumulates in the incubation mixtures. Oxygen strongly inhibits the same step, especially in the microsomal fraction. Phenobarbital treatment stimulates primarily the reduction of p-nitrobenzoic acid to p-hydroxyaminobenzoic acid by microsomes. p-Nitrobenzoic acid reductases of the supernatant fraction and of microsomes display different properties with respect to inhibition by oxygen and stimulation by phenobarbital. ACKNOWLEDGMENT The authors wish to express their gratitude to Dr. I Suzuki, Department of Synthetic Chemistry, National Institute of Hygienic Sciences, for his kind supply of p-hydroxyaminobenzoic acid and guidance in its synthesis. ER -