The preferred route of kynurenine metabolism in the rat

Bender, David A.; McCreanor, G. M.

doi:10.1016/0304-4165(82)90379-8

Cited by 70 publications

(43 citation statements)

References 11 publications

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“…On the other hand, there is some evidence indicating that some kynurenines may impair energy metabolism, by altering oxygen consumption in heart mitochondria. This is interesting since some enzymes that catalyze the kynurenine pathway are located in the inner membrane of the mitochondria or inside this organelle, implying that kynurenines may have a direct and/or an indirect effect on the mitochondrial bioenergetics (Brown, 1971;Okamoto, 1971;Bender and McCreanor, 1982). Baran et al (2001) demonstrated that kynurenic acid (KA) affected dose-dependently the respiratory parameters of heart mitochondria, reducing significantly the respiratory control and P/O values.…”

Section: Discussionmentioning

confidence: 98%

Kynurenines Impair Energy Metabolism in Rat Cerebral Cortex

et al. 2006

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Growing evidence indicates that some metabolites derived from the kynurenine pathway, the major route of L-tryptophan catabolism, are involved in the neurotoxicity associated with several brain disorders, such as Huntington's disease, Parkinson's disease and Alzheimer's disease, as well as in glutaryl-CoA dehydrogenase deficiency (GAI). Considering that the pathophysiology of the brain damage in these neurodegenerative disorders is not completely defined, in the present study, we investigated the in vitro effect of L-kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HA) and anthranilic acid (AA) on some parameters of energy metabolism, namely glucose uptake, 14CO2 production from [U-14C] glucose, [1-14C] acetate and [1,5-14C] citrate, as well as on the activities of the respiratory chain complexes I-IV and Na+,K+-ATPase activity in cerebral cortex from 30-day-old rats. We observed that all compounds tested, except L-kynurenine, significantly increased glucose uptake and inhibited 14CO2 production from [U-14C] glucose, [1-14C] acetate and [1,5-14C] citrate. In addition, the activities of complexes I, II and IV of the respiratory chain were significantly inhibited by 3HK, while 3HA inhibited complexes I and II activities and AA inhibited complexes I-III activities. Moreover, Na+,K+-ATPase activity was not modified by these kynurenines. Taken together, our present data provide evidence that various kynurenine intermediates provoke impairment of brain energy metabolism.

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Section: Discussionmentioning

confidence: 98%

Kynurenines Impair Energy Metabolism in Rat Cerebral Cortex

et al. 2006

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“…3-HAA is known as one of the main free radicals generators due to is able to generate ROS throughout its autooxidation [77, 78]. This autooxidation process first consists in the production of anthraniloyl radical, which is oxidized to the quinoneimine.…”

Section: Different Actions Of Kynurenine Catabo-lites In the Brainmentioning

confidence: 99%

The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia

Cuartero

Parra²,

García‐Culebras³

et al. 2016

CPD

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Kynurenines are a wide range of catabolites which derive from tryptophan through the “Kynurenine Pathway” (KP). In addition to its peripheral role, increasing evidence shows a role of the KP in the central nervous system (CNS), mediating both physiological and pathological functions. Indeed, an imbalance in this route has been associated with several neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. Altered KP catabolism has also been described during both acute and chronic phases of stroke; however the contribution of the KP to the pathophysiology of acute ischemic damage and of post-stroke disorders during the chronic phase including depression and vascular dementia, and the exact mechanisms implicated in the regulation of the KP after stroke are not well established yet. A better understanding of the regulation and activity of the KP after stroke could provide new pharmacological tools in both acute and chronic phases of stroke. In this review, we will make an overview of CNS modulation by the KP. We will detail the KP contribution in the ischemic damage, how the unbalance of the KP might trigger an alteration of the cognitive function after stroke as well as potential targets for the development of new drugs.

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“…Homogeneous L-kynurenine 3-hydroxylase exhibits a monomer of 145,000 M, (Nishimoto et al, 1979). Bender and McCreanor (1982) showed that although the pathway leading to pyridine nucleotides in rat liver is regulated by the activity of tryptophan 2,3-dioxygenase, the activity of L-kynurenine 3-hydroxylase might be also rate-limiting. The same investigators showed that, upon kinetic measurements, the more usually accepted pathway of mitochondrial hydroxylation, followed by the kynureninase action (i.e., the hydrolysis to 3-hydroxyanthranylate; see below), is likely to predominate in the rat.…”

Section: B Aerobic Pathwaymentioning

confidence: 99%