| Kynurenines and the respiratory parameters on rat heart mitochondria. | |
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MedLine Citation:
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PMID: 12505541 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It has been shown recently that the L-kynurenine metabolite kynurenic acid lowers the efficacy of mitochondria ATP synthesis by significantly increasing state IV, and reducing respiratory control index and ADP/oxygen ratio of glutamate/malate-consuming heart mitochondria. In the present study we investigated the effect of L-tryptophan (1.25 microM to 5 mM) and other metabolites of L-kynurenine as 3-hydroxykynurenine (1.25 microM to 2.5 mM), anthranilic acid (1.25 microM to 5 mM) and 3-hydroxyanthranilic acid (1.25 microM to 5 mM) on the heart mitochondria function. Mitochondria were incubated with saturating concentrations of respiratory substrates glutamate/malate (5 mM), succinate (10 mM) or NADH (1 mM) in the presence or absence of L-tryptophan metabolites. Among tested substances, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and anthranilic acid but not tryptophan affected the respiratory parameters dose-dependently, however at a high concentration, of a micro molar range. 3-Hydroxykynurenine and 3-hydroxyanthranilic acid lowered respiratory control index and ADP/oxygen ratio in the presence of glutamate/malate and succinate but not with NADH. While, anthranilic acid reduced state III oxygen consumption rate and lowered the respiratory control index only of glutamate/malate-consuming heart mitochondria. Co-application of anthranilic acid and kynurenic acid (125 or 625 microM each) to glutamate/malate-consuming heart mitochondria caused a non-additive deterioration of the respiratory parameters determined predominantly by kynurenic acid. Accumulated data indicate that within L-tryptophan metabolites kynurenic acid is the most effective, followed by anthranilic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid to influence the respiratory parameters of heart mitochondria. Present data allow to speculate that changes of kynurenic acid and/or anthranilic acid formation in heart tissue mitochondria due to fluctuation of L-kynurenine metabolism may be of functional importance for cardiovascular processes. On the other hand, beside the effect of 3-hydroxyanthranilic acid and 3-hydroxykynurenine on respiratory parameters, their oxidative reactivity may contribute to impairment of mitochondria function, too. |
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Authors:
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H Baran; K Staniek; B Kepplinger; J Stur; M Draxler; H Nohl |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Life sciences Volume: 72 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2002-12-30 Completed Date: 2003-02-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: England |
Other Details:
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Languages: eng Pagination: 1103-15 Citation Subset: IM |
Affiliation:
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Institute of Pharmacology and Toxicology, Veterinary University Vienna, A-1210 Vienna, Austria. Halina.Baran@vu-wien.ac.at |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3-Hydroxyanthranilic Acid
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pharmacology Animals Anthranilic Acids / pharmacology Free Radical Scavengers / pharmacology Kinetics Kynurenine / analogs & derivatives*, pharmacology* Male Mitochondria, Heart / drug effects, metabolism* Mitochondrial Proteins / metabolism NAD / metabolism Oxygen Consumption / drug effects* Rats Rats, Sprague-Dawley Succinates / metabolism Tryptophan / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anthranilic Acids; 0/Free Radical Scavengers; 0/Mitochondrial Proteins; 0/Succinates; 118-92-3/anthranilic acid; 343-65-7/Kynurenine; 484-78-6/3-hydroxykynurenine; 53-84-9/NAD; 548-93-6/3-Hydroxyanthranilic Acid; 73-22-3/Tryptophan |
| Comments/Corrections | |
Erratum In:
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Life Sci. 2003 Jul 4;73(7):953 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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