SELECTIVE INHIBITION OF NICOTINAMIDE ADENINE DINUCLEOTIDE DEPENDENT OXIDATION BY 2-METHYL-3-o-TOLYL-4-QUINAZOLONE

Abstract

The effect of 2-methyl-3-o-tolyl-4-quinazolone (QZ-2) on the respiratory activity of rat brain homogenate and isolated mitochondria was investigated. QZ-2 selectively inhibited NAD-dependent oxidations of substrates of the tricarboxylic acid cycle, L-glutamate and β-hydroxybutyrate, while the oxidation of sodium succinate and NADH, independent of NAD, were unaffected. Increase in the concentration of QZ-2 increased the inhibition. Added NAD increased the respiratory activity of rat brain homogenate and isolated mitochondria during oxidation of sodium citrate, DL-isocitrate, α-ketoglutarate, L-malate, L-glutamate, and β-hydroxybutyrate. The inhibition produced by QZ-2 during such oxidation was reduced by the presence of added NAD. It seems that QZ-2 acts at a point before the entrance of electrons from succinic dehydrogenase and NADH to cytochrome b in the respiratory chain.