Glyceraldehyde 3-phosphate oxidation

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 ... 

In the payoff phase, each of the two molecules of glyceraldehyde 3-phosphate derived from glucose undergoes oxidation at C-l the energy of this oxidation reaction is conserved in the formation of one NADH and two ATP per triose phosphate oxidized. The net equation for the overall process is... 

Another assay for phosphoffuctokinase involves converting the fructose 1,6-diphosphate to dihydroxyacetone phosphate and glyceraldehyde 3-phosphate with aldolase, equilibrating the triosephosphates with triosephosphate isomerase, and then measuring the production of NADH on the oxidation of the glyceraldehyde phosphate by glyceraldehyde 3-phosphate dehydrogenase. 

The preceding reactions yield two molecules of NADPH and one molecule of ribose 5-phosphate for each molecule of glucose 6-phosphate oxidized. However, many cells need NADPH for reductive biosyntheses much more than they need ribose 5-phosphate for incorporation into nucleotides and nucleic acids. In these cases, ribose 5-phosphate is converted into glyceraldehyde 3-phosphate and fructose 6-phosphate by transketolase and transaldolase. These enzymes create a reversible link between the pentose phosphate pathway and glycolysis by catalyzing these three successive reactions. 

Glyceraldehyde phosphate dehydrogenase probably holds the distinction of being the classic thiol enzyme in the minds of most biochemists . The thiol is believed to be involved in the initial attachment of the aldehyde substrate as a thiohemiacetal. The em me-bound thiohemiacetal is then oxidized by NAD generating an enzyme-bound thioester. In more sophisticated proposals for this mechanism the nicotinamide cofactor interacts with the active centre thiol as a charge transfer type of complex. This facilitates the reaction of the thiol with the carbonyl of the substrate. The thiol addition and the electron transfer to nicotinamide occur... 

This molecular complexity is intriguing and must have a physiological meaning. Kaplan and his associates have proposed the following explanation. In skeletal muscle the main function of LDH is to convert pyruvate to lactate for the purpose of oxidizing the NADH generated by glyceraldehyde phosphate oxida-... 

The second half of the glycolytic pathway involves the reactions that convert the metabolic energy in the glucose molecule into ATP. Altogether, four new ATP molecules are produced. If two are considered to offset the two ATPs consumed in phase 1, a net yield of 2 ATPs per glucose is realized. Phase II starts with the oxidation of glyceraldehyde-3-phosphate, a reaction with a large... 

Oxidation of 2 molecules of glyceraldehyde-3-phosphate yields 2 NADH Pyruvate conversion to acetyl-CoA (mitochondria) 2 NADH Citric acid cycle (mitochondria) 2 molecules of GTP from 2 molecules of succinyl-CoA + 2 + 2... 

Glyceraldehyde 3-phosphate is oxidized to a carboxylic acid and then phosphorylated to yield 1,3-bisphosphoglycerate. 

Figure 29.10 Mechanism of Step 6 in Figure 29.7, the oxidation and phosphorylation of glyceraldehyde 3-phosphate to give 1,3-bisphosphoglycerate.

It can function anaerobically by regenerating oxidized NAD (required in the glyceraldehyde-3-phosphate dehydrogenase reaction) by reducing pymvate to lactate. 

Baker, M.S., Feigan, J. and Lowther, D.A. (1989). The mechanisms of chondrocyte hydrogen peroxide damage. Depletion of intracellular ATP due to suppression of glycolysis caused by oxidation of glyceraldehyde-3-phosphate dehydrogenase. J. Rheumatol. 16, 7-14. 

Pihl, A., and Lange, R. (1962) The interaction of oxidized glutathione, cystamine mono-sulfoxide, and tetrathionate with the -SH groups of rabbit muscle D-glyceraldehyde 3-phosphate./. Biol. Chem. 237, 1356-1362. 

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