Xanthurenic acid from tryptophan metabolism

The second quinoline derivative produced in animal metabolism is xanthurenic acid, which was isolated by Musajo (M12). Xanthurenic acid (4,8-dihydroxyquinoline-2-carboxylic acid) also originates from tryptophan through kynurenine (M13). 

Vitamin Be deficiency symptoms include dermatitis, a microcytic, hypochromic anemia, weakness, irritability, and, in some cases, convulsions. Xanthurenic acid (a degradation product of tryptophan) and other compounds appear in the urine because of an inability to completely metabolize amino acids. A decreased ability to synthesize heme from glycine may cause the microcytic anemia (see Chapter 44), and decreased decarboxylation of amino acids to form neurotransmitters (see Chapter 48) may explain the convulsions. 

If the dietary levels of niacin and tryptophan are insufficient, the condition known as pellagra results. The symptoms of pellagra are dermatitis, diarrhea, dementia, and, finally, death. In addition, abnormal metabolism of tryptophan occurs in a vitamin B6 deficiency. Kynurenine intermediates in tryptophan degradation cannot be cleaved because kynureninase requires PLP derived from vitamin B6. Consequently, these intermediates enter a minor pathway for tryptophan metabolism that produces xanthurenic acid, which is excreted in the urine. 

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). 

Rose [305] reported the excretion of grossly increased amounts of xanthurenic acid in the urine of women taking combination products. A similar increase in tryptophan metabolites occurs in pregnancy and has been interpreted as indicating pyridoxine deficiency [306]. Dewhurst [307] subsequently postulated a causal connection between dysfunction of trytophan metabolism and certain types of depression. Winston [308] developed the concept further by suggesting that depression from oral contraceptive medication be treated with pyridoxine. Price and Toseland [309] have proposed routine inclusion of pyridoxine in oral contraceptive preparations. Developments will be awaited with interest. 

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