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

TitleEffects of cadmium and mercury on the upper part of skeletal muscle glycolysis in mice.
Publication TypeJournal Article
Year of Publication2014
AuthorsRamírez-Bajo, Maria José, de Atauri Pedro, Ortega Fernando, Westerhoff Hans V., Gelpí Josep Lluis, Centelles Josep J., and Cascante Marta
JournalPLoS One
Volume9
Paginatione80018
Date Published2014
ISSN1932-6203
KeywordsAnimals, Cadmium, Fructosephosphates, Glucose, Glucose-6-Phosphate, Glycolysis, Hexokinase, In Vitro Techniques, Inbred C57BL, Mercury, Mice, Muscle, Phosphofructokinase-1, Phosphofructokinases, Skeletal
Abstract

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.

DOI10.1371/journal.pone.0080018