Document Detail

Kynurenines and the respiratory parameters on rat heart mitochondria.
MedLine Citation:
PMID:  12505541     Owner:  NLM     Status:  MEDLINE    
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.
H Baran; K Staniek; B Kepplinger; J Stur; M Draxler; H Nohl
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Life sciences     Volume:  72     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2002-12-30     Completed Date:  2003-02-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1103-15     Citation Subset:  IM    
Institute of Pharmacology and Toxicology, Veterinary University Vienna, A-1210 Vienna, Austria.
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MeSH Terms
3-Hydroxyanthranilic Acid / pharmacology
Anthranilic Acids / pharmacology
Free Radical Scavengers / pharmacology
Kynurenine / analogs & derivatives*,  pharmacology*
Mitochondria, Heart / drug effects,  metabolism*
Mitochondrial Proteins / metabolism
NAD / metabolism
Oxygen Consumption / drug effects*
Rats, Sprague-Dawley
Succinates / metabolism
Tryptophan / pharmacology
Reg. No./Substance:
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
Erratum In:
Life Sci. 2003 Jul 4;73(7):953

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