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UMR 8601 CNRS, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris, France.
Biochimie. 2022 Aug;199:150-157. doi: 10.1016/j.biochi.2022.04.009. Epub 2022 Apr 22.
The kynurenine pathway of l-tryptophan metabolism produces several compounds of high physiological importance in the central nervous system and the immune response. Among them, cinnabarinic acid (CA) which results from the condensation of two molecules of 3-hydroxy-anthranilic acid has been identified as an activator of the metabotropic glutamate receptor (mGluR4) and the aryl hydrocarbon receptor (AhR). However, very few information was available about its stability under physiological conditions. This article shows that CA is unstable even under very soft conditions mimicking physiological conditions. Incubations in phosphate buffer pH 7.4 lead to several products coming from various reactions such as addition of HO on its quinone imine function, decarboxylation, and deamination. Moreover, CA rapidly reacts with glutathione (GSH), leading to adducts that result from the Michael type addition of this physiological nucleophile on the quinone imine function of CA. These preliminary results indicate that the great reactivity of CA and the nature of its various products should be considered when studying its activity towards any biological target.
色氨酸代谢的犬尿氨酸途径在中枢神经系统和免疫反应中产生几种具有重要生理意义的化合物。其中，肉桂酰基犬尿氨酸（CA）是由两个 3-羟基邻氨基苯甲酸分子缩合而成的，已被鉴定为代谢型谷氨酸受体（mGluR4）和芳烃受体（AhR）的激活剂。然而，关于其在生理条件下的稳定性的信息却很少。本文表明，CA 即使在模拟生理条件的非常温和的条件下也不稳定。在 pH 值为 7.4 的磷酸盐缓冲液中的孵育导致了几种产物的生成，这些产物来自于各种反应，如醌亚胺功能上的 HO 加成、脱羧和脱氨。此外，CA 与谷胱甘肽（GSH）快速反应，生成加合物，这是由于这种生理亲核试剂在 CA 的醌亚胺功能上进行迈克尔型加成。这些初步结果表明，在研究 CA 对任何生物靶标的活性时，应考虑 CA 的高反应性及其各种产物的性质。
