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.
References:
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- Cosi C, Mannaioni G, Cozzi A, et al. G-protein coupled receptor 35 (GPR35) activation and inflammatory pain: Studies on the antinociceptive effects of kynurenic acid and zaprinast. Neuropharmacology. 2011;60(7-8):1227-1231.
- Pawlak K, Mysliwiec M, Pawlak D. Kynurenine pathway - a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients. Adv Med Sci. 2010;55(2):196-203.
- Lugo-Huitron R, Blanco-Ayala T, Ugalde-Muniz P, et al. On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress. Neurotoxicol Teratol. 2011;33(5):538-547.
- Bender DA, Njagi EN, Danielian PS. Tryptophan metabolism in vitamin B6-deficient mice. Br J Nutr. 1990;63(1):27-36.
- Rios-Avila L, Coats B, Chi Y-Y, et al. Metabolite Profile Analysis Reveals Association of Vitamin B-6 with Metabolites Related to One-Carbon Metabolism and Tryptophan Catabolism but Not with Biomarkers of Inflammation in Oral Contraceptive Users and Reveals the Effects of Oral Contraceptives on These Processes. J Nutr. 2015;145(1):87-95.
- Brown RR, Yess N, Price JM, Linkswiler H, Swan P, Hankes LV. Vitamin B6 Depletion in Man: Urinary Excretion of Quinolinic Acid and Niacin Metabolites. J Nutr. 1965;87(4):419-423.
- Theofylaktopoulou D, Ulvik A, Midttun Ø, et al. Vitamins B 2 and B 6 as determinants of kynurenines and related markers of interferon-γ-mediated immune activation in the communitybased Hordaland Health Study. Br J Nutr. 2014;112(7):1065-1072.
- Rose D, Toseland P. Urinary excretion of quinolinic acid and other tryptophan metabolites after deoxypyridoxine or oral contraceptive administration. Metabolism. 1973;22(2):165-171.
- Davis I, Liu A. What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics? Expert Rev Neurotherap. 2015;15(7):719-721.
- Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13(7):465-477.
- Zheng P, Chen JJ, Huang T, et al. A novel urinary metabolite signature for diagnosing major depressive disorder. J Proteome Res. 2013;12(12):5904-5911.
- Oxenkrug G. Serotonin-kynurenine hypothesis of depression: historical overview and recent developments. Curr Drug Targets. 2013;14(5):514-521.
- Rider LG, Schiffenbauer AS, Zito M, et al. Neopterin and quinolinic acid are surrogate measures of disease activity in the juvenile idiopathic inflammatory myopathies. Clin Chem. 2002;48(10):1681-1688.
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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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1-Methylhistidine, 1-Methylhistidine (Plasma), 2-,3-, and 4-Methylhippuric acid, 2-Methylhippuric Acid, 2-Methylsuccinic Acid, 3,4-Dihydroxyhydrocinnamic Acid, 3,5-Dihydroxybenzoic Acid, 3-Methylhistidine (Plasma), 3-Phenylpropionylglycine, 4-Hydroxybenzoic Acid, 4-Hydroxyphenylacetic Acid, 4-Hydroxyphenylpyruvic Acid, 5-Hydroxyindoleacetic Acid, 8-Hydroxy-2'-deoxyguanosine, a-Hydroxybutyric Acid, a-Keto-b-methylvaleric Acid, a-Ketobutyric Acid, a-Ketoglutaric Acid, a-Ketoisocaproic Acid, a-Ketoisovaleric Acid, a-Aminoadipic Acid (Plasma), Adipic Acid, Alanine, Alanine (Plasma), Aldosterone, Anserine (Plasma), Anthranilic Acid, Arabinitol, Arginine (Plasma), Arginosuccinic Acid, Arginosuccinic Acid (Plasma), Asparagine (Plasma), Aspartic Acid (Plasma), b-Hydroxybutyric Acid, b-Hydroxyisovaleric Acid, b-Alanine (Plasma), Benzoic Acid, Benzoylform, Branched Chain Alpha-Keto Organic Acids, Carnosine, Carnosine (Plasma), cis-Aconitic Acid, Citric Acid, Citrulline (Plasma), Cortisol, Cortisone, Creatinine, Cystathionine (Plasma), Cystine (Plasma), D-Lactic Acid, Equol, Ethanolamine (Plasma), Ethylmalonic Acid, Formiminoglutamic Acid, Fructose, Fumaric Acid, g-Aminobutyric Acid (Plasma), Glucaric Acid, Glucose, Glutamic Acid (Plasma), Glutamine (Plasma), Glutamine / Glutamate Ratio (Plasma), Glutaric Acid, Glycine (Plasma), Glycylproline (Plasma), Hexanoylglycine, Hippuric Acid, Histidine (Plasma), Homocitrulline (Plasma), Homocystine (Plasma), Homogentisic Acid, Homovanillic Acid, Hydroxykynurenine, Hydroxyproline, Hydroxyproline (Plasma), Indoleacetic Acid, Isocitric Acid, Isoleucine/allo-Isoleucine (Plasma), KT Ratio, KT Ratio (Plasma), Kynurenic Acid, Kynurenine, Kynurenine (Plasma), Lactic Acid, Leucine (Plasma), Lysine (Plasma), Malic Acid, Mandelic Acid, Methionine (Plasma), Methylmalonic Acid, Microalbumin, Ornithine, Ornithine (Plasma), Orotic Acid, Oxalic Acid, pH, Phenylacetic Acid, Phenylalanine (Plasma), Phosphate, Phosphoethanolamine (Plasma), Picolinic Acid, Pimelic Acid, Proline (Plasma), Pyridoxic Acid, Pyroglutamic Acid, Pyruvic Acid, Quercetin, Quinolinic Acid, Sarcosine (Plasma), Sebacic Acid, Serine (Plasma), Suberic Acid, Suberylglycine, Succinic Acid, Sulfocysteine (Plasma), Tartaric Acid, Taurine (Plasma), Threonine (Plasma), Total Branched Chain Amino Acids (Plasma), Tryptophan, Tryptophan (Plasma), Tyrosine, Tyrosine (Plasma), Valine (Plasma), Vannilylmandelic Acid, Xanthurenic Acid
