Neurospora, 3-hydroxyanthranilic acid

The results with Neurospora led Bonner and Yanofsky (94) to suggest that the conversion of hydroxyanthranilic acid to nicotinic acid went by way of Intermediates A and B of diagram 21. Quinolinic acid formation was thought to be a shunt or side reaction of intermediate A, slow conversion to nicotinic acid possibly providing an alternative pathway. A similar conclusion was drawn from experiments in the rat (971), and it is now generally agreed that the conversion of quinolinic acid to nicotinic acid is at best of the order of a side reaction (e.g., 685, 754, and in man, 397, 696). 

An alternative route to nicotinic acid involves scission of hydroxyanthranilic acid between carbons 2 and 3, with intermediate formation of isocin-chomeronic acid (diagram 21). But the latter does not act as a nicotinic precursor in Neurospora (374), and this route can probably be excluded. 

Hydroxykynurenine has been postulated as the intermediate between kynurenine and 3-hydroxyanthraniIic acid in Neurospora. It is highly active in replacing niacin for several niacinless Neurospora strains. No mutant has been found which can use 3-hydroxyanthranilic acid that cannot use 3-hydroxykynurenine. 

In studies with Neurospora, it has been found that 3-hydroxyanthranilic acid accumulates in the culture medium filtrates of one niacinless strain, and can satisfy the niacin requirement of another strain. ... 

A number of experiments have been carried out with to establish that the amino nitrogen of 3-hydroxyanthranilic acid is the precursor of the pyridine ring nitrogen. In one of these experiments a mutant strain of Neurospora utilizing 3-hydroxyanthranilic acid for growth... 

This conversion has been found to be catalyzed by an enzyme isolated from the liver and kidney of several mammalian species (6Jir67), from tryptophan-adapted Pseudomonas (68, 69), and from Neurospora (60). The enzyme appears to be identical with the system which causes the hydrolysis of 3-kynurenine to anthranilic acid. The products of the hydrolysis of hydroxykynurenine are hydroxyanthranilic acid and alanine. Pyri-doxal phosphate is required for the reaction. 

Evidence that 3-hydroxyanthranilic acid was a precursor of nicotinic acid was obtained from the observations of Mitchell and Nyc (61) that the compound could replace the nicotinic acid requirements of some Neurospora mutants. Bonner (62) has isolated a mutant which spedfi[Pg.634]

These studies were confirmed by tracer experiments showing that nitrogen of nicotinic acid (formed by Neurospora) is derived from 3-hydroxyanthranilic acid (478). Experiments with doubly labeled tryptophan demonstrate that tryptophan is probably the only source of quinolinic acid in rat metabolism (645) and that carbon atom 3 of tryptophan, the precursor of the carboxyl carbon of 3-hydroxyanthranilic acid, becomes carboxyl carbon in nicotinic acid (310,340,341,373). In vitro studies of the enzymic oxidation of 3-hydroxyanthranilic acid confirm its relationship to quinolinic acid (498) and show that picolinic acid may also form from it (539,540) but nicotinic acid synthesis under... 

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