PEP, Phosphoenolpyruvate

FIGURE 3.13 Phosphoenolpyruvate (PEP) is produced by the euolase reaction (hi glycolysis see Chapter 19) and hi turn drives the phosphorylation of ADP to form ATP in the pyruvate kinase reaction. 

FIGURE 20.24 Phosphoenolpyruvate (PEP) carboxylase, pyrnvate carboxylase, and malic enzyme catalyze anaplerotlc reactions, replenishing TCA cycle Intermediates. 

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.

Three types of synthases catalyze the addition of phosphoenolpyruvate (PEP) to aldoses or the corresponding terminal phosphate esters. By concurrent release of inorganic phosphate from the preformed enolate nucleophile, the additions are essentially irreversible. None of the enzymes are yet commercially available and little data are available oil the individual specificities for the aldehydic substrates. A bacterial NeuAc synthase (EC 4.1.3.19) has been used for the microscale synthesis of A -acetylncuraminic acid from Af-acetyl-D-mannosamine31 and its 9-azido analog from 2-acetamido-6-azido-2,6-dideoxy-D-mannose32. 

Two heterocyclic phosphonates have been designed and synthesized in an attempt to identify more spatially conHned, planar analogs of glyphosate than obtained previously with the pyridine analog 111 (75). Molecular modeling experiments suggest that 5-phosphono-thiazolin-2-one 133 and 5-phosphono-l,2,4-triazolin-3-one 137 each may overlap either with glyphosate or its known competitive substrate, phosphoenolpyruvate (PEP), very well (5). 

Aldolases catalyze asymmetric aldol reactions via either Schiff base formation (type I aldolase) or activation by Zn2+ (type II aldolase) (Figure 1.16). The most common natural donors of aldoalses are dihydroxyacetone phosphate (DHAP), pyruvate/phosphoenolpyruvate (PEP), acetaldehyde and glycine (Figure 1.17) [71], When acetaldehyde is used as the donor, 2-deoxyribose-5-phosphate aldolases (DERAs) are able to catalyze a sequential aldol reaction to form 2,4-didexoyhexoses [72,73]. Aldolases have been used to synthesize a variety of carbohydrates and derivatives, such as azasugars, cyclitols and densely functionalized chiral linear or cyclic molecules [74,75]. 

The bacterial phosphoenolpyruvate (PEP)-dependent carbohydrate phosphotransferase systems (PTS) are characterised by their unique mechanism of group translocation. The transported solute is chemically modified (i.e. phos-phorylated) during the process (for comprehensive reviews see [151,152] and... 

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. 

Pyruvate kinase the last enzyme in aerobic glycolysis, it catalyzes a substrate-level phosphorylation of ADP using the high-energy substrate phosphoenolpyruvate (PEP). Pyruvate kinase is activated by fructose 1,6-bisphosphate from the PFK-1 reaction (feedforward activation). 

Bisphosphoglycerate and phosphoenolpyruvate (PEP) are high-energy intermediates used to generate ATP by substrate-level phosphorylation. 

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. 

C4 plants incorporate CO2 by the carboxylation of phosphoenolpyruvate (PEP) via the enzyme PEP carboxylase to make the molecule oxaloacetate which has 4 carbon atoms (hence C4). The carboxylation product is transported from the outer layer of mesophyll cells to the inner layer of bundle sheath cells, which are able to concentrate CO2, so that most of the CO2 is fixed with relatively little carbon fractionation. 

Hydroxycyclopropanecarboxylic acid phosphate HCP 34 is an analogue of phosphoenolpyruvate (PEP) 35 which is metabolized by various enzymes. HCP 34 is a potent competitive inhibitor of enzymes utilizing PEP 35, such as PEP carboxylase, enolase, pyruvate kinase, and probably other enzymes. It is a substantially better inhibitor than phospholactate 36 or phosphoglycolate 37, presumably because of the similarity of its geometric and electronic structures with phosphoenol pyruvate,Eq. 12 [28]. 

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... 

Some bacteria uhlize phosphoenolpyruvate (PEP 71)-dependent lyases for the generation of sialic acids and related compounds (Scheme 2.2.5.4) [1]. By simultaneous release of inorganic phosphate from the preformed enolpyruvate nucleo-... 

Synthetic studies for sialic acid and its modifications have extensively used the catabolic enzyme N-acetylneuraminic acid aldolase (NeuA E.C. 4.1.3.3), which catalyzes the reversible addition of pyruvate (70) to N-acetyl-D-mannosamine (ManNAc, 11) to form the parent sialic acid N-acetylneuraminic acid (NeuSNAc, 12 Scheme 2.2.5.23) [1, 2, 45]. In contrast, the N-acetylneuraminic acid synthase (NeuS E.C. 4.1.3.19) has practically been ignored, although it holds considerable synthetic potential in that the enzyme utilizes phosphoenolpyruvate (PEP, 71) as a preformed enol nucleophile from which release of inorganic phosphate during... 

Fig. 2.6. Regulation of Phosphofructokinase from Bacillus stearothermophilus. The tetrameric phosphofructokinase is aUostericaUy regulated by ADP, Frc-6-phosphate, and phosphoenolpyruvate (PEP). The binding of ADP and Frc-6-phosphate converts the enzyme into the active R state. PEP binds to the T state and inhibits phosphofructokinase. The circles represent the R state, and the squares represent the T state of the enzyme.

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) ... 

The other anaplerotic reactions shown in Table 16-2 are also regulated to keep the level of intermediates high enough to support the activity of the citric acid cycle. Phosphoenolpyruvate (PEP) carboxylase, for example, is activated by the glycolytic intermediate fructose 1,6-bisphosphate, which accumulates when the citric acid cycle operates too slowly to process the pyruvate generated by glycolysis. 

The first "roadblock" to overcome in the synthesis of glucose from pyruvate is the irreversible conversion in glycolysis of pyruvate to phosphoenolpyruvate (PEP) by pyruvate kinase. In gluconeogenesis, pyruvate is first carboxylated by pyruvate carboxylase to oxaloacetate (OAA), which is then converted to PEP by the action of PEP-carboxykinase (Figure 10.3). 

Pyruvate is converted to phosphoenolpyruvate (PEP) by pyruvate carboxylase and PEP carboxykinase. The carboxylase requires biotin and ATP, and is allosterically activated by acetyl CoA. PEP carboxykinase, which requires GTP, is the rate-limiting step in gluconeo genesis. The transcription of its mRNA is increased by glucagon and decreased by insulin. 

In this one-pot procedure NeuAc 16 is generated from ManNAc 15 and pyruvic acid in situ with sialic acid aldolase and then converted irreversibly to CMP-NeuAc 17. CMP is converted to CDP with myokinase and ATP. The released ADP is converted to ATP with pyruvate kinase and PEP. CDP is then converted to CTP also with pyruvate kinase and phosphoenolpyruvate (PEP). The formed CTP reacts with NeuAc catalyzed by NeuAc synthetase to give 17. 

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