Hypothesis kynurenic and quinolinic acids: The main players of the kynurenine pathway and opponents in inflammatory disease
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I hypothesize that the intermediates of the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) degradation kynurenic acid (KA) and quinolinic acid (QA) play opposite roles in inflammatory diseases, with KA being antiinflammatory and QA being immunosuppressant. Darlington et al. have demonstrated a decrease in the ratio of plasma 3-hydroxyanthranilic acid to anthranilic acid ([3-HAA]/[AA]) in many inflammatory conditions and proposed that this decrease either reflects inflammatory disease or is an antiinflammatory response. I argue in favour of the latter possibility and provide evidence that KA is responsible for the decrease in this ratio by increasing AA formation from Kyn through activation of the kynureninase reaction. Immunosuppression has been attributed to some Kyn metabolites tested at concentrations far greater than could occur in microenvironments. So far, only QA has been shown using immunohistochemistry to reach immunosuppressive levels. Future immune studies of the KP should focus on QA as the potentially main microenvironmentally measurable immunosuppressant and should include KA as an antiinflammatory metabolite.
Badawy, A.A.B. (2018) 'Hypothesis kynurenic and quinolinic acids: The main players of the kynurenine pathway and opponents in inflammatory disease', Medical Hypotheses, 118, pp.129-138. DOI: 10.1016/j.mehy.2018.06.021.
Article published in Medical Hypotheses on 21 June 2018, available at: https://doi.org/10.1016/j.mehy.2018.06.021.
Cardiff Metropolitan University (Grant ID: Cardiff Metropolian (Internal))
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