Glycolysis triose phosphates

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... 

This reaction is followed by another phosphorylation with ATP catalyzed by the enzyme phosphofructoki-nase (phosphofructokinase-1), forming fructose 1,6-bisphosphate. The phosphofructokinase reaction may be considered to be functionally irreversible under physiologic conditions it is both inducible and subject to allosteric regulation and has a major role in regulating the rate of glycolysis. Fructose 1,6-bisphosphate is cleaved by aldolase (fructose 1,6-bisphosphate aldolase) into two triose phosphates, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate are inter-converted by the enzyme phosphotriose isomerase. 

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 is converted to pyruvate via glycolysis. 5 6. Oxoacids are converted to pyruvate and then acetyl-CoA, as shown in Chapter 8 (see Figure 8.8). 

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. 

In the preparatory phase of glycolysis, ATP is invested to convert glucose to fructose 1,6-bisphosphate. The bond between C-3 and C-4 is then broken to yield two molecules of triose phosphate. 

Now let us consider the further conversion of PEP and of the triose phosphates to glucose 1-phosphate, the key intermediate in biosynthesis of other sugars and polysaccharides. The conversion of PEP to glucose 1-P represents a reversal of part of the glycolysis sequence. It is convenient to discuss this along with gluconeogenesis, the reversal of the complete glycolysis sequence from lactic acid. This is an essential part of the Cori cycle (Section F) in our own bodies, and the same process may be used to convert pyruvate derived from deamination of alanine or serine (Chapter 24) into carbohydrates. 

Fructose-1,6-bisphosphate and the Two Triose Phosphates Constitute the Second Metabolic Pool in Glycolysis... 

The metabolic pool that consists of fructose-1,6-bisphosphate and the two triose phosphates—glyceralde-hyde-3-phosphate and dihydroxyacetone phosphate (DHAP)—is somewhat different from the other two pools of intermediates in glycolysis because of the nature of the chemical relationships between these compounds. In the other pools the relative concentrations of the component compounds at equilibrium are independent of the absolute concentrations. Because of the cleavage of one substrate into two products, the relative concentrations of fructose-1,6-bisphosphate and the triose phosphates are functions of the actual concentrations. For such reactions, the relative concentrations of the split products must increase with dilution. (For the reaction A v B + C, the equilibrium constant is equal to [B][C]/[A], If the concentration of A decreases, for example, by a factor of 4, equilibrium is... 

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... 

Alternatively, it is possible to write a sequence of reactions, including the action of phosphofructokinase and aldolase on seven-carbon intermediates, in which the carbon of ribulose-5-phosphate is converted mainly to glyceralde-hyde-3-phosphate. Such a pathway, with the triose phosphate entering the glycolytic sequence, amounts to a bypass, or shunt, around the first reactions of glycolysis, and the name hexose monophosphate shunt is sometimes used. Any amount of ribose-5-phosphate or erythrose-4-phosphate that may be needed for biosynthetic sequences can also be ob-... 

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. 

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