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2016 ; 9
(ä): 17-29
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Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain,
Liver and Heart Mitochondria
#MMPMID27226722
Baran H
; Staniek K
; Bertignol-Spörr M
; Attam M
; Kronsteiner C
; Kepplinger B
Int J Tryptophan Res
2016[]; 9
(ä): 17-29
PMID27226722
show ga
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.