How does arsenate inhibit cellular respiration?
Arsenic inhibits different mitochondrial enzymes and disconnects oxidative phosphorylation, thereby impairing cellular respiration.
What is the mechanism of arsenic poisoning?
One of the mechanisms by which arsenic exerts its toxic effect is through impairment of cellular respiration by the inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation leading to cell death [119], [120].
Which enzyme in glycolysis is affected by arsenate?
enzyme glyceraldehyde-3-phosphate dehydrogenase
The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase works as an arsenate reductase in human red blood cells and rat liver cytosol.
How does arsenate affect TCA cycle?
Arsenic interferes with the activity of the TCA cycle by inhibiting the α-ketoglutarate dehydrogenase complex, which requires the activity of the sulfhydryl group associated with the dihydrolipoamide moiety of the enzyme complex.
How does arsenic affect NADH?
These results suggest that arsenite activates NADH oxidase to produce superoxide, which then causes oxidative DNA damage. The result that arsenite at low concentrations increases oxidant levels and causes oxidative DNA damage in vascular smooth muscle cells may be important in arsenic-induced atherosclerosis.
Why is arsenate toxic to cells?
Arsenate is toxic to bacteria because, as an analog of phosphate, it is transported by bacterial phosphate transport systems and interferes intracellularly with production of phosphorylated intermediates.
What enzyme is inhibited by arsenate?
Arsenite inhibits the PDH complex by binding to the lipoic acid moiety. MMAIII was shown to be a more potent inhibitor of the PDH complex than iAsIII. The PDH complex oxidizes pyruvate to acetyl-CoA, a precursor to intermediates of the citric acid cycle.
Why does arsenate affect glycolysis?
Arsenate inhibits ATP formation during glycolysis by substituting arsenate for the phosphate anion in a process known as arsenolysis. In one of the steps of glycolysis, the phosphate group is enzymatically linked to D-gylceraldehyde-3-phosphate to form 1,3-diphospho-D-glycerate.
Does arsenic increase NADH levels?
Therefore, we examined the effect of arsenite at 1 to 10 μmol/L levels on DNA integrity of human VSMCs. The results show that arsenite at this concentration range can increase NADH oxidase activity and induce DNA strand breaks.