Effects of cadmium and mercury on the upper part of skeletal muscle glycolysis in mice

The effects of pre-incubation with mercury (Hg(2+)) and cadmium (Cd(2+)) on the activities of individual glycolytic enzymes, on the flux and on internal metabolite concentrations of the upper part of glycolysis were investigated in mouse muscle extracts. In the range of metal concentrations analysed...

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Bibliographic Details
Published in:PloS one 2014-01, Vol.9 (1), p.e80018
Main Authors: Ramírez-Bajo, Maria José, de Atauri, Pedro, Ortega, Fernando, Westerhoff, Hans V, Gelpí, Josep Lluis, Centelles, Josep J, Cascante, Marta
Format: Article
Language:English
Subjects:
Analysis
Animal models
Animals
Aparell locomotor
Biochemistry
Biology
Cadmi
Cadmium
Cadmium - toxicity
Chemistry
Dehydrogenases
Enzims
Enzymatic activity
Enzyme activity
Enzymes
Experiments
Fluctuations
Flux
Fructose
Fructose-6-phosphate
Fructosephosphates - metabolism
Glucose
Glucose - metabolism
Glucose-6-phosphate
Glucose-6-Phosphate - metabolism
Glucòlisi
Glycolysis
Glycolysis - drug effects
Heavy metals
Hexokinase
Hexokinase - metabolism
In Vitro Techniques
Incubation
Inhibition
Kinases
Laboratories
Mathematical models
Mercuri
Mercury
Mercury (metal)
Mercury - toxicity
Metabolism
Metabolites
Metal concentrations
Mice
Mice, Inbred C57BL
Molecular biology
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Muscles
Musculoskeletal system
Phosphates
Phosphofructokinase
Phosphofructokinase-1 - metabolism
Phosphofructokinases - metabolism
Physiology
Proteins
Ratolins
Skeletal muscle
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Summary:The effects of pre-incubation with mercury (Hg(2+)) and cadmium (Cd(2+)) on the activities of individual glycolytic enzymes, on the flux and on internal metabolite concentrations of the upper part of glycolysis were investigated in mouse muscle extracts. In the range of metal concentrations analysed we found that only hexokinase and phosphofructokinase, the enzymes that shared the control of the flux, were inhibited by Hg(2+) and Cd(2+). The concentrations of the internal metabolites glucose-6-phosphate and fructose-6-phosphate did not change significantly when Hg(2+) and Cd(2+) were added. A mathematical model was constructed to explore the mechanisms of inhibition of Hg(2+) and Cd(2+) on hexokinase and phosphofructokinase. Equations derived from detailed mechanistic models for each inhibition were fitted to the experimental data. In a concentration-dependent manner these equations describe the observed inhibition of enzyme activity. Under the conditions analysed, the integral model showed that the simultaneous inhibition of hexokinase and phosphofructokinase explains the observation that the concentrations of glucose-6-phosphate and fructose-6-phosphate did not change as the heavy metals decreased the glycolytic flux.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0080018