Glyceraldehyde-3-phosphate GAP

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.

Scheme 2.2.2.2 DXP synthase transfers a C2 group(hydroxyethyl) from pyruvate to acceptor compounds as D-glyceraldehyde 3-phosphate (GAP) or D-glyceraldehyde with an intermediate ThDP-bound stage. The reaction is drawn to the products side by decarboxylation, which is a virtually irreversible reaction.

Step 4 of Figure 29.7 Cleavage Fructose 1,6-bisphosphate is cleaved in step 4 into two 3-carbon pieces, dihydroxyacetone phosphate (DH.4P) and glyceraldehyde 3-phosphate (GAP). The bond between C3 and C4 of fructose i,6-bisphosphale... 

The second stage of glycolysis begins with the splitting of fructose 1,6-bisphosphate into glyceraldehyde 3-phosphate GAP) and dihydroxyacetone phosphate DHAP). The products of the remaining steps in glycolysis consist of three-carbon units rather than six-carbon units. 

An enzyme that has been the subject of intensive experimental and theoretical studies is triosephosphate isomerase (TIM), which catalyses the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP), an essential step in the glycolytic pathway (Fersht 1985). The mechanism of the enzyme has been examined by QM/MM calculations which we do not describe here because it falls outside the topic ofthis review (Bash et al. 1991). However, an additional aspect of the overall mechanism is the conformational change of an 11-residue loop region (residues 166-176) which moves more than 7 A and closes over the active site when substrate binds (Joseph et al. 1990 Lolis et al. 1990). Mutagenesis experiments have... 

Fructose-l,6-diphosphate (FDP) may also be converted into dihydroxyacetone phosphate (DHAP), which is also synthesized from glyceraldehyde-3-phosphate (GAP). The dihydroxyacetone phosphate (DHAP), thus obtained, is converted into glycerol-3-phosphate (G-3-P), in the presence of cytosolic NADH. The latter gives away one phosphate radical to ADP to generate ATP and glycerol (Chart 1). Thus in the above process, one mole of glucose is converted into two moles of pyruvate with a net gain of two moles of ATP [1],... 

Glyceraldehyde may be converted to the glycolytic intermediate, glyceraldehyde 3-phosphate (GAP), by the action of the enzyme triokinase. This enzyme phosphorylates glyceraldehyde at the expense of another molecule of ATP. The GAP can then enter into the glycolytic pathway and be further converted to pyra-vate, or recombine with DHAP to form F16BP by the action of aldolase. 

Triose Phosphate Isomerase Diffusional Encounters with D-Glyceraldehyde-3-Phosphate In this section we use a real system, triose phosphate isomerase (TIM) and its substrate D-glyceraldehyde—3-phosphate (GAP) to demonstrate the capabilities of Brownian dynamics simulations with electrostatics. TIM is a glycolytic enzyme that catalyzes the interconversion of GAP and dihydroxy-acetone phosphate (DHAP). It has been described as an almost perfea catalyst because of its remarkable efficiency. Structurally, TIM is a dimeric enzyme consisting of two identical polypeptide chains of 247 amino acid residues. Each subunit consists of eight loop-p/loop-a units and contains one aaive site. Located near each aaive site is a peptide loop, which is mobile in the native enzyme and folds down to cover the active site when the substrate is bound. Kinetically, the reaction appears to be diffusion controlled and proceeds with a measured rate constant of 4.8 x 10 M s L TIM has consequently been the focus of many kinetic and struaural studies. ... 

Glyceraldehyde-3-phosphate dehydrogenase is an example of an enzyme that uses NAD as an oxidizing coenzyme. The enzyme catalyzes the oxidation of the aldehyde group of glyceraldehyde-3-phosphate (GAP) to an anhydride of a carboxylic acid and phosphoric acid. This is a reaction that occurs in glycolysis (Figure 25.3). 

---