Xanthurenic acid biosynthesis

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). 

Two metabolites which were called trididemnic acids A (167) and B (168), were isolated from a Northeast Pacific ascidian Trididemnum sp. [127]. Xanthurenic acid (169) co-occurred with the trididemnic acids suggesting biosynthesis from tryptophane no activity data was reported. 

Quinolobactin, 8-hydroxy-4-methoxy-2-quinoline carboxylic acid, is an alkaloid produced by Pseudomonas fluorescens ATCC17400. The biosynthesis of quinolobactin involves the tryptophan-kynurenine-xanthurenic acid pathway (Figure 6.13). 

The experiments discussed above on the biosynthesis of a pseudan have also shown that kynurenic acid is not the precursor of the 2-alkylquinolin-4(lH)-ones. Based on the putative function of the genes of the qbs operons (176), a pathway was proposed for the biosynthesis of kynurenic acid (I), xanthurenic acid [10(8)], and quinolobactin [IO(8) j in Pseudomonas fluorescens ATCC 17400 (Scheme 5). The first step, the oxidation of tryptophan to N-formylkynurenine, is likely to be catalyzed by the enzyme tryptophan 2,3-dioxygenase (TDO) (QbsF), which is a heme-dependent enzyme. The second step, the deformylation of N-formyl-kynurenine to L-kynurenine is catalyzed by kynurenine formamidase (KFA). The product of qbsH, a metal-dependent hydrolase found also in other bacterial genomes, is the likely candidate. 

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