Arsenate, glyceraldehyde-3-phosphate

Glyceraldehyde-phosphate dehydrogenase arsenate and, 44 193-194 Glycerol, as matrix liquid, 28 5 Glyceiol-3-phosphate dehydrogenase, 44 206, 207... 

The idea that enzymes whose normal substrate is orthophosphate can use arsenate in its place, and that the esters of arsenate formed are rapidly hydrolyzed, was given by Braunstein (16) in 1931, to explain the effects of arsenate on glycolysis. This idea was formulated more precisely for glyceraldehyde-phosphate dehydrogenase in 1939. This enzyme, E—SH, normally oxidizes its aldehyde substrate with phosphate uptake to give an acyl phosphate, as follows ... 

Arsenic, in its arsenate (AsO ") form prevents the se quential transformation of glyceraldehyde 3-P to 3-P glycerate (D-5). Arsenate resembles phosphate and can substitute for it in oxidative phosphorylation, and also attach to glyceraldehyde 3-P, in place of phosphate. The resultant unstable arsenate compound does change to the normal end result, 3-P-glycerate, but without the normal production of an ATP. This is poisonous. 

The inhibitory effects of heavy metals, and of cyanide on cytochrome oxidase and of arsenate on glyceraldehyde phosphate dehydrogenase, are examples of non-competitive inhibition. This type of inhibitor acts by combining with the enzyme in such a way that for some reason the active site is rendered inoperative. The inhibition may or may not be reversible but it is not affected by the addition of extra substrate. 

Arsenate will replace phosphate in all phospho-rolytic reactions, e.g., in the cleavage of glycogen by glycogen phosphorylase, of sucrose by sucrose phosphorylase, and in the action of purine nucleoside phosphorylase.b Glucose 1-arsenate or ribose-1-arsenate is presumably a transient intermediate which is hydrolyzed to glucose. The overall process is called arsenolysis. Another reaction in which arsenate can replace phosphate is the oxidation of glyceraldehyde 3-phosphate in the presence of P to form 1,3-bisphosphoglycerate ... 

Gregus, Z. and Nemeti, B. (2005) The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase works as an arsenate reductase in human red blood cells and rat liver cytosol. Toxicological Sciences, 85(2), 859-69. 

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