Formation of kynurenic and xanthurenic acids from kynurenine and 3-hydroxykynurenine in the dinoflagellate Lingulodinium polyedrum: role of a novel, oxidative pathway.

The dinoflagellate Lingulodinium polyedrum (syn. Gonyaulax polyedra) was used as a model organism for studying the effects of high and low physiological oxidative stress on the formation of kynurenic and xanthurenic acids from kynurenine and 3-hydroxykynurenine. Cell were incubated with the precursors and exposed to light (high physiological stress due to photosynthetically formed oxidants) or kept in darkness (low stress). In cultures of less than 0.5 ml cell volume/l of medium, cells took up approximately one half of 0.1 mM extracellular kynurenine within 18 h. The amino acid was partially converted to kynurenic acid, most of which was released to the medium; however, intracellular concentrations of the product were by approximately 10-fold higher than extracellular levels. Rates of kynurenic acid release exceeded by far those explained by kynurenine and tryptophan aminotransferase activities, the latter representing an additional source of kynurenic acid formation via indole-3-pyruvic acid. Light enhanced the release of kynurenic acid by approximately 4-fold; these rates were further increased by exposure to continuous light. Diurnal rhythmicity of kynurenic acid release was clearly exogenous and did not match with the circadian pattern of kynurenine or tryptophan aminotransferase activities; no rhythm was detected in constant darkness. Similar findings were obtained on turnover of 3-hydroxykynurenine to xanthurenic acid and release of the product to the medium. However, light/dark differences were relatively smaller, and additional products were formed, according to HPLC data obtained with electrochemical detection. Results are most easily explained on the basis of a recently discovered pathway of kynurenic acid formation from kynurenine, involving either non-enzymatic oxidation by H(2)O(2) or, at higher rates, enzymatic catalysis by hemoperoxidase. A corresponding mechanism may exist for the hydroxylated analogue.