Glyceraldehydes 3-phosphate

In a reversible reaction, glyceraldehyde 3-phosphate is converted by glyceraldehyde phosphate dehydrogenase to an energy-rich intermediate, 1,3-bisglycerophosphate (or 3-phosphoglyceroyl-phosphate). 

Glyceraldehyde 3-phosphate is oxidized by NAD+, and inorganic phosphate (Pi) is incorporated into the product to form an acyl phosphate, 1,3-bisphosphoglycerate. NAD+ is reduced by transfer of a hydride ion (H ) from thiohemiacetal to the fourth position on the nicotinamide ring of NAD.  

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This cleavage is a retro aldol reaction It is the reverse of the process by which d fruc tose 1 6 diphosphate would be formed by aldol addition of the enolate of dihydroxy acetone phosphate to d glyceraldehyde 3 phosphate The enzyme aldolase catalyzes both the aldol addition of the two components and m glycolysis the retro aldol cleavage of D fructose 1 6 diphosphate... 

Further steps m glycolysis use the d glyceraldehyde 3 phosphate formed m the aldolase catalyzed cleavage reaction as a substrate Its coproduct dihydroxyacetone phosphate is not wasted however The enzyme triose phosphate isomerase converts dihydroxyacetone phosphate to d glyceraldehyde 3 phosphate which enters the glycol ysis pathway for further transformations... 

Suggest a reasonable structure for the intermediate in the con ] version of dihydroxyacetone phosphate to o glyceraldehyde 3 phosphate J... 

TKsubstrate pNZYTffiS IN ORGANIC SYNTHESIS] (Vol 9) D-Glyceraldehyde-3-phosphate[591-57-l]aldolase-cataly zed additions... 

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

The TK-catalyzed reaction requires the presence of thiamine pyrophosphate and Mg " as cofactors. Although the substrate specificity of the enzyme has not been thoroughly investigated, it has been shown that the enzyme accepts a wide variety of 2-hydroxyaldehydes including D-glyceraldehyde 3-phosphate [591-57-1], D-glyceraldehyde [453-17-8], D-ribose 5-phosphate /47(9(9-2%/7, D-erythrose 4-phosphate and D-erythrose [583-50-6] (139,149—151). 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

Figure 3 A possible mechanism for the isomerization of dihydroxyacetone phosphate (DHAP) to D glyceraldehyde 3 phosphate (GAP) by the enzyme triosephosphate isomerase (TIM). The general acid (Glu 165) and general base (His 95) are shown.

A non-linear regression analysis is employed using die Solver in Microsoft Excel spreadsheet to determine die values of and in die following examples. Example 1-5 (Chapter 1) involves the enzymatic reaction in the conversion of urea to ammonia and carbon dioxide and Example 11-1 deals with the interconversion of D-glyceraldehyde 3-Phosphate and dihydroxyacetone phosphate. The Solver (EXAMPLEll-l.xls and EXAMPLEll-3.xls) uses the Michaehs-Menten (MM) formula to compute v i- The residual sums of squares between Vg(,j, and v j is then calculated. Using guessed values of and the Solver uses a search optimization technique to determine MM parameters. The values of and in Example 11-1 are ... 

Figures 11-7 and 11-8 show plots of velocity versus substrate concentration of the interconversion of D-glyceraldehyde 3-Phosphate, and the conversion of urea, respectively.

Pyruvate, Citrate, Succinate, Glyceraldehyde-3-phosphate, Fructose-1,6-bisphosphate, 3-PhosphogIyceric acid... 

FIGURE 6.34 Sheet structures formed from andparallel arrangements of /3-strands, (a) Streptomyces suh i x Xu inhibitor, (b) glutathione reductase domain 3, and (c) the second domain of glyceraldehyde-3-phosphate dehydrogenase represent minimal andparallel /S-sheet domain structures. In each of these cases, an andparallel /S-sheet is largely exposed to solvent on one face and covered by helices and random coils on the other face. (Jane Richardson)... 

Thus far, we have considered enzyme-catalyzed reactions involving one or two substrates. How are the kinetics described in those cases in which more than two substrates participate in the reaction An example might be the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (Chapter 19) ... 

Phosphorylation of glucose and conversion to 2 molecules of glyceraldehyde-3-phosphate ... 

The triose phosphate isomerase reaction completes the first phase of glycolysis, each glucose that passes through being converted to two molecules of glyceraldehyde-3-phosphate. Although the last two steps of the pathway are... 

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... 

Dihydroxyacetone phosphate is of course an intermediate in glycolysis. D-Gly-ceraldehyde can be phosphorylated by triose kinase in the presence of ATP to form D-glyceraldehyde-3-phosphate, another glycolytic intermediate. 

How might iodoacetic acid affect the glyceraldehyde-3-phosphate dehydrogenase reaction in glycolysis Justify your answer. 

NAD (P) " -dependent enzymes are stereospecific. Malate dehydrogenase, for example, transfers a hydride to die pro-/ position of NADH, whereas glyceraldehyde-3-phosphate dehydrogenase transfers a hydride to die pro-5 position of the nicotinamide. Alcohol dehydrogenase removes a hydride from the pro-i position of edianol and transfers it to die pro-i position of NADH. 

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