Quinolinic Acid (Quinolinate) is a breakdown product of hydroxykynurenine via QPR transferase.
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.
- Excessive quinolinic acid production has been correlated with other neuroinflammatory markers.
- Increased xanthurenic acid and quinolinic acid, plus a decrease in kynurenic acid seen in ASD cases.
- Phthalates structurally mimic tryptophan metabolites. High phthalate exposure increased urinary concentrations of quinolinic acid.
- Elevated levels of kynurenic acid, xanthurenic acid, and quinolinic acid were found in patients with metabolic syndrome.
- Decreased picolinic acid and increased quinolinic acid blood levels reported in suicidal subjects.
- Niacin (B3) is a product of tryptophan degradation. In alcoholic pellagra patients, kynurenic acid increased, and xanthurenic acid and quinolinic acid decreased.
References:
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- 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.
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- 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.
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- 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.
Quinolinic Acid
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