Triose phosphate isomerase glycolysis

Fig. 8.22. Isomerases rearrange atoms within a molecule. In the pathway of glycolysis, triose phosphate isomerase converts dihydroxyacetone phosphate to glyceraldehydes 3-phos-phate by rearranging hydrogen atoms. No other substrates or products of the reaction exist.

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... 

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... 

Triose phosphate isomerase (TPI) catalyzes the interconversion of glyceralde-hyde-3-phosphate and dihydoxyacetone phosphate and has an important role in glycolysis, gluconeogenesis, fatty acid synthesis, and the hexose monophosphate pathway. Red blood cell TPI activity measured in vitro is approximately 1000 times that of Hx, the least active glycolytic enzyme. TPI is a dimer of identical subunits, each of molecular weight 27,000, and does not utilize cofactors or metal ions. Posttranslational modification of one or both subunits may occur by deamidination, resulting in multiple forms of the enzymes and creating a complex multibanded pattern on electrophoresis. 

Triose phosphate isomerase is one of the enzymes of glycolysis (see Section 15.2) and is responsible for converting dihydroxyacetone phosphate into glyceraldehyde 3-phosphate by a two-stage enolization process. An intermediate enediol is involved - this common enol can revert to a keto form in two ways, thus providing the means of isomerization. 

The reaction mechanism is similar to the reaction promoted by phosphohexose isomerase in step (2) of glycolysis (Fig. 14-4). After the triose phosphate isomerase reaction, C-1, C-2, and C-3 of the starting glucose are chemically indistinguishable from C-6, C-5, and C-4, respectively (Fig. 14-6), setting up the efficient metabolism of the entire six-carbon glucose molecule. 

The isomeric triose phosphates, glyceraldehyde-3-phos-phate and dihydroxyacetone phosphate, bear the same relationship to each other as do glucose-6-phosphate and fruc-tose-6-phosphate. Their interconversion, catalyzed by triose phosphate isomerase, is equally facile (see fig. 12.13). Dihydroxyacetone phosphate is a starting material for the synthesis of the glycerol moiety of fats (chapter 19), but only glyceraldehyde-3-phosphate is used in glycolysis. Thus, under ordinary circumstances nearly all of the dihydroxyacetone phosphate that is formed in the cleavage of... 

Fructose 1-phosphate is then split into glyceraldehyde and dihy-droxyacetone phosphate by fructose 1-phosphate aldolase. The dihydroxy-acetone feeds into glycolysis at the triose phosphate isomerase step (Fig. 1). 

PEP is converted to fructose 1,6-bisphosphate in a series of steps that are a direct reversal of those in glycolysis (see Topic J3), using the enzymes enolase, phosphoglycerate mutase, phosphoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase, triose phosphate isomerase and aldolase (see Fig 1). This sequence of reactions uses one ATP and one NADH for each PEP molecule metabolized. 

Answer Problem 1 outlines the steps in glycolysis involving fructose 1,6-bisphosphate, glyceraldehyde 3-phosphate, and dihydroxyacetone phosphate. Keep in mind that the aldolase reaction is readily reversible and the triose phosphate isomerase reaction catalyzes extremely rapid interconversion of its substrates. Thus, the label at C-l of glyceraldehyde 3-phosphate would equilibrate with C-l of dihydroxyacetone phosphate (AG ° = 7.5 kJ/mol). Because the aldolase reaction has AG ° = -23.8 kJ/mol in the direction of hexose formation, fructose 1,6-bisphosphate would be readily formed, and labeled in C-3 and C-4 (see Fig. 14-6). 

Two metabolic patterns are discernible from the results. Carbon atoms 2, 1, and 7 of shikimate (VI) are derived almost equally from G-1,6, G-2,5, and G-3,4, respectively. In the Embden-Meyerhof pathway of hexose metabolism (see Fig. 2), D-fructose 1,6-diphosphate is cleaved to 1,3-dihydroxy-2-propanone phosphate (G-1,2,3) and D-glycerose 3-phosphate (G-4,5,6), and the two trioses are interconverted by triose phosphate isomerase. The observed randomization of label between Cl and C6, C2 and C5, and C3 and C4 of hexose therefore implies that C2, Cl, and C7 of shikimate are derived from a 3-carbon intermediate of glycolysis. The small but significant preponderance of G-6 over G-1, of G-5 over G-2, and, presumably, of G-4 over G-3, can be explained by recent observations that, in the aldolase cleavage of D-fructose 1,6-diphosphate, the 1,3-dihy-... 

Keep in mind that, because of the actions of aldolase and triose phosphate isomerase, two molecules of glyceraldehyde 3-phosphate were formed and hence two molecules of ATP were generated. These ATP molecules make up for the two molecules of ATP consumed in the first stage of glycolysis. 

Glyceraldehyde 3-phosphate continues on in the glycolysis pathway, but dihydroxyacetone phosphate is first isomerized by the enzyme triose phosphate isomerase. As in the glucose-to-fructose conversion of step 2, the... 

Enzyme Mechanisms.— Triose phosphate isomerase has been a popular enzyme recently, having been the chief example quoted in two reviews on perfection and efficiency in enzyme catalysis - and the subject of seven successive papers in one issue of Biochemistry including one on the evolution of enzyme function and the development of catalytic efficiency. During glycolysis in muscle, fructose 1,6-bisphos-... 

Glyceraldehyde 3-phosphate is on the direct pathway of glycolysis, whereas dihydroxyacetone phosphate is not. Unless a means exists to convert dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, a three-carbon fragment useful for generating ATP will be lost. These compounds are isomers that can be readily interconverted dihydroxyacetone phosphate is a ketose, whereas glyceraldehyde 3-phosphate is an aldose. The isomerization of these three-carbon phosphory-lated sugars is catalyzed by triose phosphate isomerase (TIM ... 

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