Abstract
The tryptophan metabolite, quinolinic (2,3-pyridinedicarboxylic) acid, is known as an endogenous neurotoxin. Quinolinic acid can form coordination complexes with iron or copper. The effects of quinolinic acid on reactive oxygen species production in the presence of iron or copper were explored by a combination of chemical assays, classical site-specific and ascorbic acid-free variants of the deoxyribose degradation assay, and mass spectrometry (ESI–MS). Quinolinic acid showed evident antioxidant activity in chemical assays, but the effect was more pronounced in the presence of copper as transition metal catalyst than in presence of iron. Nano-ESI–MS confirmed the ability of quinolinic acid to form coordination complexes with iron(II) or copper(II) and quinolinic acid stability against oxidative attack by hydroxyl radicals. The results illustrate a highly milieu-dependent quinolinic acid chemistry when it enters reactions as competitive ligand.
Highlights
Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN) (Fig. 1) is a metabolic intermediate of tryptophan catabolism within the kynurenine pathway
QUIN was added as competitive ligand to the reaction solution, an antioxidant effect was more pronounced in case of copper than in case of iron
These results suggest that possible detrimental effects of copper can be quenched more efficiently than those of iron
Summary
Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN) (Fig. 1) is a metabolic intermediate of tryptophan catabolism within the kynurenine pathway. A few decades ago, kynurenines were suggested to act as important endogenous modulators of various brain functions [1]. The ratio among QUIN, 3-hydroxykynurenine and kynurenic acid can affect cognitive performance and neuronal vulnerability, among others. Kynurenines can participate in many neurodegenerative diseases and neurological impairments associated with some infectious diseases, such as AIDS or brain malaria [2,3]. QUIN has been explored extensively for its effects on brain functions [4e6]. A higher than physiological concentration (below 100 nM) has been found in brains or cerebrospinal fluids of patients suffering from Alzheimer's or Huntington's disease, amyotrophic lateral sclerosis, depression, autism and schizophrenia [5,6].
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