3-hydroxyanthranilic Acid Metabolism

The participation of 3-hydroxyanthranilic acid as an intermediate in the biosynthesis of nicotinic acid from tryptophan was first demonstrated in certain mutant strains of Neurospora in 1948 by Bonner (1) and by Mitchell and Nyc (2). In addition, Mitchell et al. (3) found that 3-hydroxyanthranilic acid can replace nicotinic acid in the nutrition of the rat. In 1946 Singal et al. (4) noted a substance in the urine of rats fed tryptophan which showed nicotinic acid activity for Lactobacillus arabinosus after being autoclaved in acid solution. This substance was later isolated and identified as quinolinic acid by Henderson (5), who also demonstrated that the excretion of quinolinic acid is increased after intraperitoneal injection of tryptophan or of 3-hydroxyanthranilic acid into rats (5, 6). It was further shown by Schweigert and Marquette (7) and by Henderson and Ramasarma (8) that quinolinic acid is the chief product formed from the incubation of 3-hydroxyanthranilic acid with rat liver homogenates and slices. The detailed chemical sequence of this conversion is of importance, not only nutritionally in the metabolism of tryptophan to nicotinic acid, but also as an example of the metabolic conversion of a benzenoid type compound to a pyridine type compound. In studying this problem, Bokman and Schweigert in 1951 (9) obtained spectrophotometric evidence for the formation of an intermediate compound in the metabolism of 3-hydroxyanthranilic acid to quinolinic acid