Unstability of cinnabarinic acid, an endogenous metabolite of tryptophan, under situations mimicking physiological conditions

Abstract

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 H₂O 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.

Keywords: Cinnabarinic acid; Michael addition; Quinone imine; Stability; Tryptophan metabolite.