Effect of 3-hydroxyanthranilic acid on the mitochondrial respiratory system

Abstract

3-Hydroxyanthranilic acid (1-0.25 m[image] inhibits the O2 uptake of rat-liver and rat-heart mitochondria respiring with nicotinamide adenine dinucleotide (NAD)-dependent substrates. This appears to be due to loss of mitochondrial NAD, and to inhibition of the [alpha]-oxoglutarate-dehydrogenase complex. 3-Hydroxyanthranilic acid does not appear to act directly on the respiratory chain. 3-Hydroxyanthranilic acid completely suppresses the activation of [alpha] -oxoglutarate oxidation either by adenosine diphosphate (ADP) in tightly coupled mitochondria or by orthophosphate in the presence of 2,4-dinitrophenol. When NAD-dependent respiratory substrates were used, the orthophosphate uptake was always more severely inhibited by 3-hydroxyanthranilic acid than was the O2 consumption. The addition of NAD prevented the inhibition of NAD-dependent oxidations (except for [alpha] -oxoglutarate oxidation), but there was no corresponding increase in orthophosphate uptake. 3-Hydroxyanthranilic acid activates the normal adenosine triphosphatase of intact mitochondria, but not the dinitrophenol-induced aJdenosine-triphosphatase activity. These effects of 3-hydroxyanthranilic acid seem to be explained by action of the substance at the level of the first respiratory chain phosphorylation.