Phosphoenolpyruvate pathway

The initial step in the pathway is the condensation of erythrose-4-phosphale with phosphoenolpyruvate, yielding dehydroquinic acid, which by elimination of the elements of water affords dehydroshikimic acid reduction of the 3-keto group to hydroxyl gives shikimic acid. 

Figure 6.24 The function of the enzyme phosphofructokinase. (a) Phosphofructokinase is a key enzyme in the gycolytic pathway, the breakdown of glucose to pyruvate. One of the end products in this pathway, phosphoenolpyruvate, is an allosteric feedback inhibitor to this enzyme and ADP is an activator, (b) Phosphofructokinase catalyzes the phosphorylation by ATP of fructose-6-phosphate to give fructose-1,6-bisphosphate. (c) Phosphoglycolate, which has a structure similar to phosphoenolpyruvate, is also an inhibitor of the enzyme.

Compartmentation of these reactions to prevent photorespiration involves the interaction of two cell types, mescrphyll cells and bundle sheath cells. The meso-phyll cells take up COg at the leaf surface, where Og is abundant, and use it to carboxylate phosphoenolpyruvate to yield OAA in a reaction catalyzed by PEP carboxylase (Figure 22.30). This four-carbon dicarboxylic acid is then either reduced to malate by an NADPH-specific malate dehydrogenase or transaminated to give aspartate in the mesophyll cells. The 4-C COg carrier (malate or aspartate) then is transported to the bundle sheath cells, where it is decarboxylated to yield COg and a 3-C product. The COg is then fixed into organic carbon by the Calvin cycle localized within the bundle sheath cells, and the 3-C product is returned to the mesophyll cells, where it is reconverted to PEP in preparation to accept another COg (Figure 22.30). Plants that use the C-4 pathway are termed C4 plants, in contrast to those plants with the conventional pathway of COg uptake (C3 plants). 

The glycolysis pathway shown in Figure 29.7 has a number of intermediates that contain phosphate groups. Why can 3-phosphoglyceryl phosphate and phosphoenolpyruvate transfer a phosphate group to ADP while glucose 6-phosphalc cannot ... 

Scheme 10.26 Partial biosynthetic pathway of fosfomycin and bialaphos. Both pathways use a homologous set of enzymes for the synthetic steps leading from phosphoenolpyruvate (PEP) to phosphonoacetaldehyde (PAA). The conversion of hydroxypropylphosphonic acid (HPP) to fosfomycin is catalyzed by the epoxidase HppE. Propenylphosphonic acid (PPA), however, is not converted to fosfomycin.

J. V. Rodriguez, J. A. Kaandorp, M. Dobrzynski, and J. K. Blom, Spatial stochastic modelling of the phosphoenolpyruvate-dependent phosphotransferase (PTS) pathway in Escherichia coli, Bioinformatics 22, 1895 (2006). 

C4 photosynthetic pathway The set of reactions through which C02 is fixed to a compound known as phosphoenolpyruvate (PEP) to yield ox-aloacetate, a four-carbon compound. 

CAM (Crassulacean Acid Metabolism) photosynthetic pathway A variant of the C4 pathway phosphoenolpyruvate fixes C02 in C4 compounds at night, and then, the fixed C02 is transferred to the ribulose bisphosphate of the Calvin cycle within the same cell during the day. Characteristic of most succulent plants, such as cacti. 

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes a critical reaction in gluconeogenesis, which under many conditions is the rate-limiting step in the pathway. A cAlVfP response element (CRE) and a glucocorticoid response element (GRE) are each located upstream from the transcription start site. 

Phosphoenolpyruvate carboxykinase (PEPCK) in the cytoplasm is induced by glucagon and cortisol. It converts OAA to phosphoenolpyruvate (PEP) in a reaction that requires GTP. PEP continues in the pathway to fructose 1,6-bisphosphate. 

Figure 6.1 Pathways involved in glucose oxidation by plant cells (a) glycolysis, (b) Krebs cycle, (c) mitochondrial cytochrome chain. Under anoxic conditions. Reactions 1, 2 and 3 of glycolysis are catalysed by lactate dehydrogenase, pyruvate decarboxylase and alcohol dehydrogenase, respectively. ATP and ADP, adenosine tri- and diphosphate NAD and NADHa, oxidized and reduced forms of nicotinamide adenine dinucleotide PGA, phosphoglyceraldehyde PEP, phosphoenolpyruvate Acetyl-CoA, acetyl coenzyme A FP, flavoprotein cyt, cytochrome e, electron. (Modified from Fitter and Hay, 2002). Reprinted with permission from Elsevier...

Enols and enolization feature prominently in some of the basic biochemical pathways (see Chapter 15). Biochemists will be familiar with the terminology enol as part of the name phosphoenolpyruvate, a metabolite of the glycolytic pathway. We shall here consider it in non-ionized form, i.e. phosphoenolpyruvic acid. As we have already noted (see Section 10.1), in the enolization between pyruvic acid and enolpyruvic acid, the equilibrium is likely to favour the keto form pyruvic acid very much. However, in phosphoenolpyruvic acid the enol hydroxyl is esterified with phosphoric acid (see Section 7.13.2), effectively freezing the enol form and preventing tautomerism back to the keto form. 

The shikimate pathway begins with a coupling of phosphoenolpyruvate (PEP) and D-erythrose 4-phosphate to give the seven-carbon 3-deoxy-D-arabino-heptulo-sonic acid 7-phosphate (DAHP) through an aldol-type condensation. Elimination of phosphoric acid from DAHP, followed by an intramolecular aldol reaction, generates the first carbocyclic intermediate, 3-dehydroquinic acid. Shikimic acid (394) is... 

Figure 1. Hypothetical mechanism for shuttling of intermediates of the common aromatic pathway between plastidic and cytosolic compartments. Enzymes denoted with an asterisk (DAHP synthase-Co, chorismate mutase-2, and cytosolic anthranilate synthase) have been demonstrated to be isozymes located in the cytosol. DAHP molecules from the cytosol are shown to be shuttled into the plastid compartment in exchange for EPSP molecules synthesized within the plastid. Abbreviations C3, phosphoenolpyruvate C4, erythrose 4-P DAHP, 3-deoxy-D-arabino-heptulosonate 7-phosphate EPSP, 5-enolpyruvylshikimate 3-phosphate CHA, chorismate ANT, anthranilate TRP, L-tryptophan PPA, prephenate AGN, L-arogenate TYR, L-tyrosine and PHE, L-phenylalanine.

Alkaloid biosynthesis needs the substrate. Substrates are derivatives of the secondary metabolism building blocks the acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose 5-phosphate (Figure 21). The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthraniUc acid as aromatized CoA ester (antraniloyl-CoA)). Shikimic acid is a product of the glycolytic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-phosphate (Figure 21). The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline and acridine. 

Fig. 1.4.1 Lactate and pyruvate metabolic pathway. (P Phosphate, PEP phosphoenolpyruvate)...

Fig. 3 Speculative metabolic schemes of the main pathways in carbohydrate metabolism in N. ovalis Abbreviations AcCoA, acetyl-CoA, Cl, complex I, Citr, citrate, FRD, fumarate reductase, FUM, fumarate, Hyd, hydrogenase, a-KG, a-ketoglutarate, MAL, malate, OXAC, oxaloacetate, PDH, pyruvate dehydrogenase, PEP, phosphoenolpyruvate carboxyk-inase, PYR, pyruvate, RQ, rhodoquinone, SUCC, succinate, SUCC-CoA, succinyl-CoA...

Vertebrates cannot convert fatty acids, or the acetate derived from them, to carbohydrates. Conversion of phosphoenolpyruvate to pyruvate (p. 532) and of pyruvate to acetyl-CoA (Fig. 16-2) are so exergonic as to be essentially irreversible. If a cell cannot convert acetate into phosphoenolpyruvate, acetate cannot serve as the starting material for the gluconeogenic pathway, which leads from phosphoenolpyruvate to glucose (see Fig. 15-15). Without this capacity, then, a cell or organism is unable to convert fuels or metabolites that are degraded to acetate (fatty acids and certain amino acids) into carbohydrates. 

Because the carbon atoms of acetate molecules that enter the citric acid cycle appear eight steps later in oxaloacetate, it might seem that this pathway could generate oxaloacetate from acetate and thus generate phosphoenolpyruvate for gluconeogenesis. However, as an examination of the stoichiometry of the citric acid cycle shows, there is no net conversion of acetate to ox-... 

All carbons are derived from either erythrose 4-phosphate (light purple) or phosphoenolpyruvate (pink). Note that the NAD+ required as a cofactor in step (3) is released unchanged it may be transiently reduced to NADH during the reaction, with formation of an oxidized reaction intermediate. Step (6) is competitively inhibited by glyphosate (COO—CH2—NH—CH2—PO ), the active ingredient in the widely used herbicide Roundup. The herbicide is relatively nontoxic to mammals, which lack this biosynthetic pathway. The chemical names quinate, shikimate, and chorismate are derived from the names of plants in which these intermediates have been found to accumulate. 

The diverse origin of two structurally similar compounds is exemplified by the (3 -lactam antibiotics isopenicillin N (1) and clavulanic acid (2). While these molecules are structurally and functionally similar, they are derived by quite different routes. Isopenicillin N is formed by the direct cyclization of the tripeptide (3) (B-80MI10400) while clavulanic acid appears to be elaborated directly from a three-carbon intermediate of the glycolytic pathway (possibly phosphoenolpyruvate, 4) and glutamic acid (5) (B-80M110401). 

Enzymatic synthesis relying on the use of aldolases offers several advantages. As opposed to chemical aldolization, aldolases usually catalyze a stereoselective aldol reaction under mild conditions there is no need for protection of functional groups and no cofactors are required. Moreover, whereas high specificity is reported for the donor substrate, broad flexibility toward the acceptor is generally observed. Finally, aldolases herein discussed do not use phosphorylated substrates, contrary to phosphoenolpyruvate-dependent aldolases involved in vivo in the biosynthetic pathway, such as KDO synthetase or DAHP synthetase [18,19]. 

---