Phosphoglycerate to Phosphoenolpyruvate

Figure 13.8 A 25-atom quantum subsystem embedded in an 8863-atom classical system to model the catalytic step in the conversion of D-2-phosphoglycerate to phosphoenolpyruvate by enolase. What factors influence the choice of where to set the boundary between the QM and MM regions Alhambra and co-workers found, using variational transition-state theory with a frozen MM region that was selected from a classical trajectory so as to make the reaction barrier and thermochemistry reasonable, that the breaking and making bond lengths were 1.75 and 1.12 A, respectively, for H, but 1.57 and 1.26 A, respectively, for D...

Elimination reactions occur in living organisms also. One important example is the conversion of 2-phosphoglycerate to phosphoenolpyruvate during the metabolism of glucose ... 

The dehydration of 2-phosphoglycerate to phosphoenolpyruvate is a critical step in the metabolism of the sugar glucose. In the following structures the circled P represents a phosphoryl group (P04 ). 

The Citric Acid Cycle (or the Tricarboxylic Acid [TCA] Cycle or the Krebsi Cycle). It will be recalled (Schemes 11.24-11.26) that the enzyme phosphoglycerate mutase (EC 5.4.2.1) acts on PGA (obtained from, e.g., fructose-1,6-bisphosphate) to produce the isomeric, 2-phosphoglycerate and that phosphopyruvate hydratase (EC 4.2.1.11) then converts the 2-phosphoglycerate to phosphoenolpyruvate. 

Then follows an elimination reaction, in which water is removed from 2-phosphoglycerate to yield phosphoenolpyruvate. 

In the second glycolytic reaction that generates a compound with high phosphoryl group transfer potential, enolase promotes reversible removal of a molecule of water from 2-phosphoglycerate to yield phosphoenolpyruvate (PEP) ... 

Enolose. A key reaction in the metabolism of sugars is the dehydration of 2-phosphoglycerate to form phosphoenolpyruvate (PEP), the phospho derivative of the enolic form of pyruvic acid ... 

The mixed anhydride of phosphoric acid and glyceric acid then is used to convert ADP to ATP and form 3-phosphoglycerate. Thereafter the sequence differs from that in photosynthesis. The next few steps accomplish the formation of pyruvate by transfer of the phosphoryi group from C3 to C2 followed by dehydration to phosphoenolpyruvate. Phosphoenolpyruvate is an effective phosphorylating agent that converts ADP to ATP and forms pyruvate ... 

Phosphoglycerate is dehydrated to phosphoenolpyruvate (PEP), which contains a high-energy enol phosphate. 

In enolase, the substrate, 2-phosphoglycerate (2-PGA) is coordinated to two Mg ions, one of which is liganded to the three conserved carboxylate residues (Asp 246, Glu 295, and Asp 320). Currently, more than 600 enolase sequences have been identified in the databases, and aU are thought to be isofunctional, catalyzing the conversion of 2-PGA to phosphoenolpyruvate. In the MLE subclass of the superfamily, at least three reactions are known to be catalysed — in addition to the lactonisation of muconate, succinylbenzoate synthase, and L-Ala-D/L-Glu epimerase reactions are observed within the 300 members. The MR subclass catalyses at least five reactions, mandelate racemisation and 4 sugar dehydratases. As in the MLE subclass, of the 400 members identified, only 50% of these are functionally assigned. 

Enolase catalyzes the trans dehydration of 2-phosphoglycerate to yield phosphoenolpyruvate and water only a small free energy change ( 1 kcal/mol) is associated with the reaction. The process is entropically driven and is readily reversible. This dimeric protein requires a divalent cation for activity and is rather promiscuous in that any one of about nine different cations can activate the enzyme (86). Depending upon the cation studied, the apoenzyme has either one or two metal binding sites per subunit. Metal ions such as Mg + and Mn + have one site per monomer, whereas Co " and Zn + will bind at two sites. In the presence of substrate there are two sites per subunit for all of the metal ions and, depending upon the pH, a third site is also induced. As the pH decreases, the third site is lost but not sites I and II. This third site is an inhibitory site, as the loss of this site parallels the loss of metal ion inhibition (87). The nature of this inhibition is not clear but may be due to the binding of the substrate at the phos-... 

The reaction, which involves removal of a water molecule from 2-phosphoglycerate to form phosphoenolpyruvate, occurs in both glycolysis and gluconeogenesis. ... 

Step 9. Dehydration of 2-phosphoglycerate to give phosphoenolpyruvate. (See Equation 17.9, page 508.)... 

Mn-SOD is an important antioxidant enzyme for the cell due to its role in detoxifying the free radical species superoxide (Oj), so HNE modification of this protein makes the cell more vulnerable to free radical attack. Alpha enolase facilitates the penultimate step of glycolysis by catalyzing the conversion of 2-phosphoglycerate into phosphoenolpyruvate. With HNE modification of alpha enolase, the cell is at risk of inadequate ATP stores due to inhibited production of pyruvate for fueling the citric acid cycle. Similarly, HNE modification of ATPase can lead to inhibited ATP formation due to the direct role of this enzyme in ATP synthesis. Triose phosphate isomerase catalyzes the reversible conversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate in glycolysis and MDH catalyzes the oxidation of malate to oxaloacetate, so HNE modification of these proteins can also lead to lower ATP production. 

For example, the hexose phosphates may be converted to sucrose, oligosaccharides, and polysaccharides such as starch and cellulose. Another example is the conversion of 3-phosphoglyceric acid to phosphoenolpyruvic acid and pyruvic acid and thence to alanine, an amino acid. 

The next step is a dehydration reaction whereby 2-phosphoglycerate is converted to phosphoenolpyruvate (PEP). The dehydration raises the group transfer potential of the phosphate group so that phosphoenolpyruvate is a high-energy compound. The reaction which is catalysed by enolase is dependent on Mg and is inhibited by fluoride. 

Other importaiit organic reaction types are elimination, oxidation-reduction, and isomerization. An elinuwuition reaction is one in which a double bond forms and a molecule such as water is removed. The dehydration of 2-phosphoglycerate to form phosphoenolpyruvate (Figure 10.11), one of the steps in carbohydrate metabolism, is an example of an elimination reaction. 

Pyruvic acid is important as an intermediate in sugar metabolism. This acid is formed as the final product of the glycolytic pathway from 3-phosphoglycerate via phosphoenolpyruvate. Pyruvic acid is also formed through the oxidative pentose phosphate cycle. The degradation of glucose in the cycle yields the C3 product glyceraldehyde 3-phosphate, which can be oxidized to pyruvate. Pyruvic acid is the principal precursor for the biosynthesis of amino acids such as alanine, as well as leucine and valine. 

In the glycolytic cycle there are three important systems responsible for the synthesis of bonds (1) the oxidation of phosphoglyceraldehyde to phosphoglyceric acid (2) the dehydration of phosphoglyceric acid to phosphoenolpyruvic acid and (3) the transfer of electrons from reduced DPN aerobically to oxygen. 

---