Establishment of the Relation between Tryptophan and Nicotinic Acid

Establishment of the Relation between Tryptophan and Nicotinic Acid 

It was only many years after the discovery of tryptophan that a plausible degradative pathway could first be outlined, but during this early period a few tryptophan metabolites were identified. The long-known (559) kynurenic acid (structure, diagram 20 cf. 408) was shown in 1904 to be derived from tryptophan (220), but the considerable amount of work on kynurenic acid formation (reviewed by Neubauer, 637) gave few useful results. Neubauer (637), however, made the plausible (and correct) suggestion that it was derived from o-aminobenzoylpyruvic acid (structure, diagram 20). 

A plausible hypothesis at this stage (about 1943) was that a sequence occurred tryptophan — an intermediate kynurenine kynurenic acid. It was thought that the intermediate between tryptophan and kynurenine might be the so-called a-hydroxytryptophan (for structure see p. 83), which had been obtained (917) on hydrolysis of phalloidine, a toxic peptide from the fungus Amanita pkalloides (567) such a pathway received 

In 1945 Elvehjem and co-workers (518) reported that nicotinic acid-deficient rats would grow if given tryptophan, suggesting conversion of tryptophan to nicotinic acid. Hosen and co-workers (731) showed that administration of tryptophan to rats increased the urinary excretion of nicotinic acid derivatives, and numerous workers confirmed the conversion of tryptophan to nicotinic acid in man (399, 667, 755) and many other species (summary, 820). In the last ten years there has been intensive investigation of tryptophan metabolism. 

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