Document Detail

Application of metabolic control analysis to the study of toxic effects of copper in muscle glycolysis.
MedLine Citation:
PMID:  10069389     Owner:  NLM     Status:  MEDLINE    
Experimental and model studies have been performed to characterise the effects of Cu2+ on the activities of individual glycolytic enzymes and on the flux and internal metabolite concentrations of the upper part of glycolysis in mouse muscle extracts. Cu2+ significantly inhibited the triosephosphate production from glucose with an IC50 of about 6.0 microM. At a similar extension Cu2+ inhibited hexokinase and phosphofructokinase, with an IC50 of 6.2 microM and 6.4 microM respectively, whereas the effects on the activities of aldolase, phosphoglucose isomerase and the internal metabolite levels were not significant. Flux control coefficients and flux response coefficients were determined in the presence of copper concentrations between 0 and 10 microM. The same values of flux control coefficients for hexokinase and for phosphofructokinase (0.8 and 0.2 respectively) were found in absence and in presence of copper. At Cu2+ equal to the flux IC50, the response coefficient was -1. The elasticity coefficients for hexokinase and phosphofructokinase at Cu2+ equal to the IC50 were also -1. A mathematical model was used to analyze the effect of copper on glycolysis under different conditions using experimental kinetic parameters and rate equations for enzymatic reactions of the upper part of glycolysis.
D Jannaschk; M Burgos; J J Centerlles; J Ovadi; M Cascante
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  445     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-04-13     Completed Date:  1999-04-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  144-8     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Spain.
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MeSH Terms
Copper / pharmacology*
Enzyme Inhibitors
Glycolysis / drug effects*
Mice, Inbred C57BL
Models, Biological
Muscle, Skeletal / drug effects*,  metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; 7440-50-8/Copper

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