Glycolysis ketose-aldose isomerization

Triose phosphate isomerase (TPI) catalyzes the ketose-aldose isomerism between glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) during glycolysis. The rate-determining step for the reaction is product dissociation. 

Glucose 6-phosphate is an important compound at the junction of several metabolic pathways (glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogenosis, and glycogenolysis). In glycolysis, it is converted to fructose 6-phosphate by phosphohexose-isomerase, which involves an aldose-ketose isomerization. 

In addition to serving as structural motifs, enols and enolates are involved in diverse biological processes. Several enol/enolate intermediates have been proposed to be involved in glycolysis (Section IV.A), wherein c/ -enediol 21 is proposed to be an intermediate in the catalytic mechanism of phosphohexose isomerase and an enol-containing enamine intermediate (22) has been proposed in the catalytic pathway of class I aldolase. In the case of glucose-fructose (aldose-ketose) isomerization, removal of the proton on Cl-OH produces the aldose while deprotonation of C2-OH yields the ketose, which is accompanied by protonation at the C2 and Cl positions, respectively. There are several cofactors that are involved in various biological reactions, such as NAD(H)/NADP(H) in redox reaction and coenzyme A in group transfer reactions. Pyridoxal phosphate (PLP, 23) is a widely distributed enzyme cofactor involved in the formation of a-keto acids, L/D-amino... 

Fructose-6-phosphate formed from the isomerization discussed above is further phos-phorylated during glycolysis to fructose-1,6-diphosphate (108), which is then cleaved by fructose-1,6-bisphosphate aldolase to afford dihydroxy acetone phosphate (109) and glyceraldehyde-3-phosphate (110). This cleavage reaction is the reverse of an aldol condensation discussed in Section II.C and during gluconeogenesis. In the latter case, fructose-1,6-bisphosphate aldolase catalyzes the reverse reaction herein via aldol condensation of the ketose 109 and the aldose 110 to form linear fructose-1,6-bisphosphate (108) . 

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 ... 

Therefore, glucose, mannose, and fructose can all be in equilibrium with the same enediol. This isomerization process occurs in biochemical reactions near pH 7 for several aldoses and ketoses in enzyme-catalyzed reactions. The isomerization of glucose and fructose occurs by way of their 6-ph osphate esters and is catalyzed by glucose 6-phosphate isomerase. The equilibrium constant for the formation of fructose 6-phosphate from glucose 6-phosphate is approximately 0.3. This reaction is one of the initial steps in glycolysis. 

---