Effects of Cadmium and Mercury on the Upper Part of Skeletal Muscle Glycolysis in Mice

Abstract

The effects of pre-incubation with mercury (Hg2+) and cadmium (Cd2+) 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 Hg2+ and Cd2+. The concentrations of the internal metabolites glucose-6-phosphate and fructose-6-phosphate did not change significantly when Hg2+ and Cd2+ were added. A mathematical model was constructed to explore the mechanisms of inhibition of Hg2+ and Cd2+ 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.

Structural and functional changes in the zebrafish (Danio rerio) skeletal muscle after cadmium exposure

“…This may be explained by the altered mitochondria structure and compromised glycogen and neutral lipid reserves (Pierron et al 2007). The observed swimming effects may also derive from direct cadmium interference on glycolytic enzymes, lactate dehydrogenase, hexokinase, and phosphofructokinase as reported (Almeida et al 2001; Ramırez-Bajo et al 2014). It can be hypothesized that, in these animals, extra energy required to maintain swimming performance is mobilized by protein catabolism (El Naga et al 2005).…”

Nutritional Aspects of Food Toxicology: Mercury Toxicity and Protective Effects of Olive Oil Hydroxytyrosol

“…The molecular mechanisms underlying Hg toxicity are related to its binding capacity to thiol groups, potentially leading to severe alteration of enzymatic as well as structural proteins [18]. Hg is a well-known inhibitor of glycolytic enzymes; in particular, Ramírez-Bajo et al report Hg inhibitory activity on both hexokinase and phosphofructokinase in mice, by reacting with crucial cysteine [19]. Furthermore, the human thioredoxin system is reported to be inhibited by Hg [20].…”

Determination of the kinetics and influence of the mercury ion on papain catalytic activity

“…11,12,17 In order to investigate the irreversible modication by Hg 2+ on papain activity, the kinetic model of substrate reaction during irreversible modication of enzyme activity described by Tsou was used to study the kinetics of papain by Hg 2+ . 11,12,17 In order to investigate the irreversible modication by Hg 2+ on papain activity, the kinetic model of substrate reaction during irreversible modication of enzyme activity described by Tsou was used to study the kinetics of papain by Hg 2+ .…”

“…Among them, mercury ions (Hg 2+ ) have attracted the most attention because of its strong toxicity and the increasing level of its extended use in industrial processes. [11][12][13] So the inhibition of enzymic activity by mercury may be a good choice as a simple, rapid and sensitive screening test. The disadvantages of these methods are the complicated operation process and expensive equipment and the need for skilled operators.…”

“…14 Papain is a cysteine protease consisting of 212 amino acid residues including seven Cys residues and is stabilized by three disulde bridges. 11,17,18 The papain assay has a wide pH for optimum activity, temperature stability and sensitiveness to heavy metals so that the papain assay is used to monitor heavy metal concentrations, including Hg 2+ , in water environments. 11,17,18 The papain assay has a wide pH for optimum activity, temperature stability and sensitiveness to heavy metals so that the papain assay is used to monitor heavy metal concentrations, including Hg 2+ , in water environments.…”