Phosphoenolpyruvic acid intermediate

Proton transfer may proceed directly or via a six-membered cyclic transition state involving a molecule of water. A calculation of the intermediate zwitter-ionic concentration for the hydrolysis of methyl phosphate monoanion, based on the pKa values for methanol and methyl phosphate dianion, predicts the first-order rate coefficient for zwitterion decomposition to be ca. 10 sec-1 at 100°C. This value is in good agreement with the observed rate of hydrolysis and, considering the assumptions involved, with the rate of P-O bond fission of the presumed zwitterionic intermediate (2) formed in the Hg(II) catalyzed solvolysis of phosphoenolpyruvic acid, a model reaction for pyruvate kinase10. 

Pyocyanin (160) is derived from the shikimate pathway, and one protein, PhzC, is equivalent to enzymes that catalyze the first step in this pathway, converting erythrose 4-phosphate (162) and phosphoenolpyruvic acid (163) to 3-deoxy-D-arabinoheptulosonate 7-phosphate (164) (Fig. 28). The equivalent enzyme in the shikimate pathway is thought to be feedback regulated, and PhzC is likely to shunt intermediates toward the shikimate pathway in preparation for pyocyanin (160)... 

The chemical properties of an enol phosphate ester are quite different from simple phosphate esters. The only important example is the glycolytic intermediate, phosphoenolpyruvic acid (Fig. III-32). 

C7H,0,oP, Mr 286.13. DAHP is an intermediate in the biosynthesis of shikimic acid and is formed by enzymatic addition of phosphoenolpyruvic acid to o- erythrose 4-phosphate by means of phospho-2-dehy-dro-3-deoxyheptanoate aldolase (DAHP synthase, EC 4.1.2.15). 

A study of the kinetics of the labeling of alanine show that its rate of labeling reaches a maximum as soon as the intermediates of the carbon reduction cycle are saturated with C . Since no secondary products of carbon photosynthesis such as sucrose are approaching saturation at this time (3-5 minutes), it appears that alanine is formed directly from intermediates of the cycle. Presumably, alanine is formed from PGA by the transamination of pyruvic acid derived from phosphoenolpyruvic acid which in turn is derived from PGA [Eq. (28)]. 

Basically, the shikimic acid pathway involves initial condensation of phosphoenolpyruvate (PEP) from the glycolysis process with erythrose-4-phosphate derived from the oxidative pentose phosphate cycle. A series of reactions leads to shikimic acid, which is then phosphorylated. The phosphorylated shikimic acid combines with a second molecule of PEP to yield prephenic acid via chorismic acid intermediate. Prephenic acid is then decarboxylated to form phenyl-pyruvate or p-hydroxyphenylpyruvate. On transamination, these two compounds yield phenylalanine and tyrosine, respectively. 

The reaction of CO2 fixation onto phosphoenolpyruvic acid by PEP carboxytransphosphorylase is considered (O Brien and Wood, 1974) as a control mechanism of propionic acid fermentation. They observed a conversion of the enzymatically active tetrameric form of PEP carboxytransphosphorylase isolated from P. shermanii into a less active dimeric form induced by oxalate, malate and fumarate. Therefore, the loss of activity by enzyme dissociation, accompanied by increased proteolysis, is an effective means of controlling the level of intermediates in propionic acid fermentation. Differential abilities of propionibacteria to fix CO2 could be associated (Wood and Leaver, 1953) with their abilities to carry out the reaction C02 Ci and to form sulfhydryl complexes with Ci. 

The free energies of hydrolysis of the phosphorylated intermediates are listed in Table I. It should be noted that with the exceptions of 1,3-diphosphoglyceric acid and phosphoenolpyruvic acid, all other sugar intermediates contain phosphate groups of low energy value. Only when these two intermediates are formed does the energy of glycolysis become available for transfer. 

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... 

Table 16-2 shows the most common anaplerotic reactions, all of which, in various tissues and organisms, convert either pyruvate or phosphoenolpyruvate to ox-aloacetate or malate. The most important anaplerotic reaction in mammalian liver and kidney is the reversible carboxylation of pyruvate by C02 to form oxaloacetate, catalyzed by pyruvate carboxylase. When the citric acid cycle is deficient in oxaloacetate or any other intermediates, pyruvate is carboxylated to produce more oxaloacetate. The enzymatic addition of a carboxyl group to pyruvate requires energy, which is supplied by ATP—the free energy required to attach a carboxyl group to pyruvate is about equal to the free energy available from ATP. 

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. 

In plants, certain invertebrates, and some microorganisms (including E. coli and yeast) acetate can serve both as an energy-rich fuel and as a source of phosphoenolpyruvate for carbohydrate synthesis. In these organisms, enzymes of the glyoxylate cycle catalyze the net conversion of acetate to succinate or other four-carbon intermediates of the citric acid cycle ... 

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). 

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

Most of the coenzymes are esters of phosphoric or pyrophosphoric acid. The main reservoirs of biochemical energy, adenosine triphosphate (ATP), creatine phosphate, and phosphoenolpyruvate are phosphates. Many intermediary metabolites are phosphate esters, and phosphates or pyrophosphates are essential intermediates in biochemical syntheses and degradations. The genetic materials DNA and RNA are phosphodiesters. 

Degradation of amino acids produces a number of intermediates, among which are a-ketoglutarate, suc-cinyl-CoA, and oxaloacetate. a-Ketoglutarate and suc-cinyl-CoA can be oxidized to oxaloacetate, but the cycle as such cannot oxidize oxaloacetate further. Oxaloacetate is oxidized further by first converting it to phosphoenolpyruvate. This permits the total oxidation of oxaloacetate to C02 by the enzymes of the TCA cycle. 

Aromatic amino acid biosynthesis proceeds via a long series of reactions, most of them concerned with the formation of the aromatic ring before branching into the specific routes to phenylalanine, tyrosine, and tryptophan. Chorismate, the common intermediate of the three aromatic amino acids, (see fig. 21.1) is derived in eight steps from erythrose-4-phosphate and phosphoenolpyruvate. We focus on the biosynthesis of tryptophan, which has been intensively studied by both geneticists and biochemists. 

Microbes and plants synthesize aromatic compounds to meet their needs of aromatic amino acids (L-Phe, L-Tyr and L-Trp) and vitamins. The biosynthesis of these aromatics [69] starts with the aldol reaction of D-erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP), which are both derived from glucose via the central metabolism, into DAHP (see Fig. 8.13). DAHP is subsequently converted, via a number of enzymatic steps, into shikimate (SA) and eventually into chorismate (CHA, see later), which is the common intermediate in the biosynthesis of the aromatic amino acids [70] and vitamins. 

Carboxylic acids. Aliphatic carboxylic acids (R—GOOH) are deprotonated at physiological pH (pH 7) and are therefore represented as R—COO. Thus, acetic acid (GHj—COOH) exists as acetate (CH3COO ) at pH 7. A variety of short chain mono-, di-and tricarboxylic acids are important intermediates in metabolism and may be present at low concentrations in all cells either as the acid or as a covalent adduct. Thus, acetate (C2) and malonate (C3) can exist as the key acyl-coenzyme A thioester intermediates acetylGoA and malonylCoA, respectively. Phosphoenolpyruvate (C3), 1,3-bisphosphoglyceric acid (C3) and 3-phosphoglyc,erate (C3) are key metabolic intermediates. 

A third fate of pyruvate is its carboxylation to oxaloacetate inside mitochondria, the first step in gluconeogenesis. This reaction and the subsequent conversion of oxaloacetate into phosphoenolpyruvate bypass an irreversible step of glycolysis and hence enable glucose to be synthesized from pyruvate. The carboxylation of pyruvate is also important for replenishing intermediates of the citric acid cycle. Acetyl CoA activates pyruvate carboxylase, enhancing the synthesis of oxaloacetate, when the citric acid cycle is slowed by a paucity of this intermediate. 

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