Kynurenic acid and Quinolinic acid are tryptophan metabolites formed through the kynurenine pathway. Tryptophan is the amino acid precursor to serotonin; its major route for catabolism is the kynurenine pathway. Important products of the kynurenine pathway include xanthurenic acid and kynurenic acid, which can further metabolize into quinolinic acid. The historical importance of this pathway has mainly been as a source of the coenzyme NAD+, which is important for all redox reactions in the mitochondria.
However, it is now understood that kynurenic and quinolinic acid have physiologic implications. This alternate pathway is upregulated in response to inflammation and stress, which can lead to deficient serotonin production. Kynurenic acid has shown some neuroprotective properties in the brain, since it can stimulate NMDA receptors. However, its importance on the periphery is still not fully elucidated. Some studies outline antiinflammatory, analgesic, antiatherogenic, antioxidative, and hepatoprotective properties to peripheral kynurenic acid.
The correlation to levels of urinary excretion needs further study. Quinolinic acid, in and of itself, can be inflammatory and neurotoxic.
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The kynurenine pathway is particularly sensitive to vitamin B6 deficiency, which can elevate urinary kynurenic acid (and xanthurenic acid).
Vitamin B2 is also an important vitamin cofactor in the enzymatic conversion reactions within the pathway.
Because a major-end product of this pathway is also NAD+, elevations in kynurenic and quinolinic acid may also reflect vitamin B3 need.
Oral contraceptives and estrogen therapy have been implicated in increasing quinolinic acid excretion both from altered tryptophan metabolism directly, as well as vitamin B6 insufficiency.
Many of the intermediates and products in the kynurenine pathway are implicated in numerous neurological and psychiatric diseases, such as depression. Alterations in this pathway also have some connection to the development of insulin resistance, diabetes, tumor growth and proliferation, and inflammatory myopathies.
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