Dihydroxyacetone phosphate Isomerization

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.

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. 

Triose phosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (see Figure 8.16). Dihydroxyacetone phosphate must be isomerized to glyceraldehyde 3-phosphate for further metabolism by the glycolytic pathway. This isomerization results in the net production of two molecules of glyceraldehyde 3-phosphate from the cleavage products of fructose 1,6-bisphosphate. 

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... 

Step 5 is an isomerization. Dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate are interconverted by the enzyme triosephosphate isomerase. 

Step 5 is an isomerization of dihydroxyacetone phosphate to glyceraldehyde 3-phosphate that occurs by keto-enol tautomerization. 

Much is known about the catalytic mechanism of triose phosphate isomerase. TIM catalyzes the transfer of a hydrogen atom from carbon 1 to carbon 2 in converting dihydroxyacetone phosphate into glyceraldehyde 3-phosphate, an intramolecular oxidation-reduction. This isomerization of a ketose into an aldose proceeds through an enediol intermediate (Figure 16.6). 

Dihydroxyacetone phosphate glyceraldehyde 3-phosphate Triose phosphate isomerase Isomerization +1.8 (+7.5) +0.6 (+2.5)... 

Glycerol formed by lipolysis is absorbed by the liver and phosphorylated, oxidized to dihydroxyacetone phosphate, and then isomerized to glyceraldehyde 3-phosphate. This molecule is an intermediate in both the glycolytic and the gluconeogenic path vays. 

An aldolase-based strategy conveniently provided access to thioketoses with sulfur in the ring. For example, RAMA-catalyzed carbon-carbon bond formation of a 3-thioglycerinaldehyde with dihydroxyacetone phosphate gave 6-thio-D-fructose 36 [32] (Figure 9.8), also available by enzymatic isomerization of 6-thio-D-glucose or 6-thio-L-sorbose with glucose isomerase (EC 5.3.1.5 vide infra) [32,41]. 

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... 

STEP S Dihydroxyacetone phosphate, one of the products of step 4, is isomerized to glyceralde-hyde 3-phosphate, the other product of step 4. 

Dihydroxyacetone phosphate is isomerized to glyceraldehyde 3-phosphate. -Enzyme triose phosphate isomerase... 

A. Dihydroxyacetone phosphate (compound I) is isomerized to glyceraldehyde 3-phosphate and converted in a series of steps to pyruvate (compound II). One of the reactions requires glyceraldehyde 3-phosphate dehydrogenase, which utilizes inorganic phosphate and produces one NADH. In the conversion of one 1,3-bisphosphoglycerate to one pyruvate, two ATP are produced. A mutase is not required. 

C. Dihydroxyacetone phosphate (Compound I) is isomerized to glyceraldehyde 3-phosphate, which is oxidized to 1,3-bisphosphoglycerate in a reaction in which inorganic phosphate and NAD+ are utilized. Then 3-phosphoglycerate (Compound II) is formed and ATP is generated. 

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