Glyceraldehyde 3-phosphate, formed from

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) . 

FIGURE 6.34 Sheet structures formed from andparallel arrangements of /3-strands, (a) Streptomyces suh i x Xu inhibitor, (b) glutathione reductase domain 3, and (c) the second domain of glyceraldehyde-3-phosphate dehydrogenase represent minimal andparallel /S-sheet domain structures. In each of these cases, an andparallel /S-sheet is largely exposed to solvent on one face and covered by helices and random coils on the other face. (Jane Richardson)... 

The isoprenoid side chains of quinones are biosynthesized mainly by the mevalonic acid pathway from acetyl-CoA. Another pathway to biosynthesizing isoprenoids is the so-called non-mevalonate ronte by which isopentenyldiphosphate (IPP) is formed from glyceraldehyde 3-phosphate and pyrnvate. The key molecule is the famesyl-diphosphate (FPP) that accepts other IPP molecules to form polyprenyl diphosphates. 

Terpenes, biogenetically, arise from two simple five-carbon moieties. Isoprenyl-diphosphate (IPP) and dimethylallyldiphosphate (DMAPP) serve as universal precursors for the biosynthesis of terpenes. They are biosynthesised from three acetylcoenzyme A moieties through mevalonic acid (MVA) via the so-called mevalonate pathway. About 10 years ago, the existence of a second pathway leading to IPP and DMAPP was discovered involving l-deoxy-D-xylulose-5-phos-phate (DXP) and 2C-methyl-D-erythritol-4-phosphate (MEP). This so-called non-mevalonate or deoxyxylulose phosphate pathway starts off with the condensation of glyceraldehyde phosphate and pyruvate affording DXP. Through a series of reactions as shown in Fig. 4.1, IPP and DMAPP are formed, respectively [3,7, 42, 43]. 

Deoxy-D-xylulose 5-phosphate is formed from the glycolytic pathway intermediates pyruvic acid and glyceraldehyde 3-phosphate with the loss of the pyruvate carboxyl (Figure 5.6). Thiamine diphosphate-mediated decarboxylation of pyruvate... 

The sugar metabolism is a source of many enzymes, the transketolase (TK) being one of them. TK transfers an a-hydroxy carbonyl fragment from D-xylu-lose-5-phosphate onto D-ribose-5-phosphate, forming D-sedoheptulose-7-phos-phate and D-glyceraldehyde-3-phosphate (Scheme 5.14). Since this reaction is an equilibrium reaction and starting materials and products are of similar stability, it is not very versatile for organic synthesis. Fortunately TK also accepts pyruvate instead of xylulose. Under these modified circumstances carbon dioxide... 

The enzyme DERA, 2-deoxyribose-5-phosphate aldolase (EC 4.1.2.4), is unique among the aldolases in that the donor is an aldehyde. In vivo it catalyzes the reversible aldol reaction of acetaldehyde and D-glyceraldehyde 3-phosphate, forming 2-deoxyribose 5-phosphate, with an equilibrium lying in the synthetic direction (Scheme 5.41). DERA, the only well-characterized member of this type I aldolase, has been isolated from both animal tissue and microorganisms.67... 

Let us consider the mechanism of glyceraldehyde 3-phosphate dehydrogenase in detail (Figure 16.8). In step 1, the aldehyde substrate reacts with the sulfhydryl group of cysteine 149 on the enzyme to form a hemithioacetal. Step 2 is the transfer of a hydride ion to a molecule of NAD + that is tightly bound to the enzyme and is adjacent to the cysteine residue. This reaction is favored by the deprotonation of the hemithioacetal by histidine 176. The products of this reaction are the reduced coenzyme NADH and a thioester intermediate. This thioester intermediate has a free energy close to that of the reactants. In step 3, orthophosphate attacks the thioester to form 1,3-BPG and free the cysteine residue. This displacement occurs only after the NADH formed from the aldehyde oxidation has left the enzyme and been replaced by a second NAD+. The positive charge on the NAD+ may help polarize the thioester intermediate to facilitate the attack by orthophosphate. 

Mode 4. Both NADPH and ATP are required. Alternatively, ribose 5-phosphate formed by the oxidative phase of the pentose phosphate pathway can be converted into pyruvate. Fructose 6-phosphate and glyceraldehyde 3-phosphate derived from ribose 5-phosphate enter the glycolytic pathway rather than reverting to glucose 6-phosphate. In this mode, ATP and NADPH are concomitantly generated, and five of the six carbons of glucose 6-phosphate emerge in pyruvate. 

Note The net result of reactions 1 through 5 is that two moles of glyceraldehyde 3-phosphate are formed from one mole of glucose. 

E. In the first three reactions of the pentose phosphate pathway, glucose is converted to ribulose 5-phosphate and C02, with the production of NADPH. These reactions are not reversible. Ribose 5-phosphate and xylulose 5-phosphate may be formed from ribulose 5-phos-phate. A series of reactions catalyzed by transketolase and transaldolase produce the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate. 

Thus, two molecules of glyceraldehyde v4-phosphate are formed from one molecule of fructose 1,6-bisphosphate by the sequential action of aldolase and triose phosphate isomerase. The economy of metabolism is evident in this reaction sequence. The isomerase funnels dihydroxyacetone phosphate into the main glycolytic pathway a separate set of reactions is not needed. 

The basic oscillatory couple exhibiting a limit cycle is F6P-FDP. Moreover, oscillations in GLU are also observed. The end product is glyceraldehyde phosphate (GAP). The first step from GLU to F6P is a first-order reaction and in the second step, an activated form of phosphofructokinase acts as an enzyme. FDP activates this second step. 

TA is also an enzyme of the oxidative pentose phosphate pathway[218). It catalyzes the transfer of the C1-C3 aldol unit from D-sedoheptulose 7-phosphate to D-Gly 3-P, and produces D-Fru 6-P and D-erythrose 4-phosphate (Fig. 14.2-3). TA forms a Schiffbase intermediate and does not require any co-factors. This enzyme is commercially available, and was used in a multi-enzyme synthesis of D-Fru from starch (Fig. 14.2-4) 1233] Here, it accomplished transfer of an aldol moiety from Fru 6-P to d-glyceraldehyde, and formed D-Gly 3-P and D-Fru. 

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