Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

• Published in: International Journal of Tryptophan Research Vol. 2016; no. 2016; pp. 17 - 29
• Main Authors: Baran, Halina, Staniek, Katrin, Bertignol-Spörr, Melanie, Attam, Martin, Kronsteiner, Carina, Kepplinger, Berthold
• Format: Journal Article
• Language: English
• Published: London, England Libertas Academica 01.01.2016; SAGE Publishing; SAGE Publications; Sage Publications Ltd. (UK); Sage Publications Ltd
• Subjects: Acids; Brain; Heart; Liver; Metabolites; Mitochondria; Mitochondrial DNA; Original Research; Physiological aspects; Tryptophan; United States; liver; xanthurenic acid; dementia; misfoldome; brain; kynurenine metabolites; respiratory parameters of mitochondria; heart
• ISSN: 1178-6469; 1178-6469
• DOI: 10.4137/IJTR.S37973

Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart mitochondria. Alterations of L-tryptophan metabolism might have an impact on the bioenergetic activities of brain, liver and/or heart mitochondria and might be involved in the development of clinical symptoms such as cardiomyopathy, hepatopathy and dementia.