Kynurenic acid from tryptophan metabolism

Our knowledge of tryptophan began some 100 years ago. In 1901 Hopkins and Cole1 isolated tryptophan from a pancreatic digest of casein. Its structure was established in 1907 by Ellinger and Flamand,2 who synthesized a substance that was identical to the tryptophan isolated by Hopkins and Cole. It is noteworthy that about 50 years prior to the discovery of tryptophan by Hopkins and Cole,1 aspects of tryptophan metabolism began to appear in the research literature, when in 1853 Liebig discovered kynurenic acid in dog urine.3 Subsequently, kynurenine, a tryptophan metabolite, was identified,4 5 and the relationship of kynurenic acid to tryptophan was understood. A brief review on the discovery of tryptophan has been described by Curzon.6... 

Hydroxyquinoline-2-carboxylic acid (kynurenic acid) was isolated from the urine of dogs (Liebig 1853). It is a metabolic product of tryptophan. 

The increased plasma kynuremne pool and the induced xanthurenic acid urinary excretion have several implications in the assessment of diazinon noncholinergic toxicity. An increase in xanthurenic acid formation may alter glucose metabolism. Xanthurenic acid has been reported to form a complex with insulin and damage pancreatic P cells. Elevated plasma kynurenin may alter kynurenin transport into the brain. Since more than 40% of brain kynurenin originates from the systemic circulation, cerebral biosynthesis of neuroactive kynurenin metabolites such as quinolinic acid and kynurenic acid may change. Finally, the availability of L-iryptophan for other L-lryptophan-dependent processes may be reduced. Tryptophan is the metabolic precursor for. serotonin and nicotinic adenine dinucleotidc. Diabetes, bladder cancer, and neurological disorders may be the toxic consequences of diazinon-altered L-tryptophan metaboli.sm (Seifert and Pewnim, 1992 Pewnim and Seifert, 1993). 

Kynurenic acid was discovered in 1853 by Liebig and has been isolated from the urine of many mammalian species. It was shown to be a metabolic product of tryptophan by Ellinger by feeding tryptophan to rats. He also proposed a structural formula for it which, however, was not quite correct. 

Role of Riboflavin. Riboflavin deficiency has been found to produce abnormaUties in the metabolism of tryptophan (307-311). The deficiency leads to an increased excretion in the urine of kynurenine, anthranilic acid, and kynurenic acid and its conjugates (308, 309). In liver and kidney slices riboflavin deficiency leads to a decrease in indolepyruvic acid accumulation and an increase in the production of kynurenic acid and anthranilic acid from L-kynurenine (310, 311). The deficiency was also found to... 

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