Phosphoenolpyruvic acid

Phosphoenolpyruvic acid tris(cyclohexylamine) salt [35556-70-8] M 465.6, m 155-180°(dec), Recrystd from aqueous Me2CO and dried in a vacuum. At 4° it is stable for >2 years and has IR at 1721cm (C=0). [Wold and Ballou J Biol Chem 227 301 7957 Clark and Kirby Biochem Prep 11 103 1966 for the monocyclohexylamine salt.]... 

The full paper has appeared on the solvolysis of the dibenzyl ester (28) of phosphoenolpyruvic acid and on the related phosphonate ester (29). Reversible phosphoryl migration from the enol oxygen to the carboxy-group occurs readily in (28) and (29) but only to a small extent - and probably not reversibly-in the monoanion (30) and phosphoenolpyruvic acid itself. These observations are readily accounted for in terms of the expected ease of pseudorotation between the various configurations of the... 

In nature, NANA arises through condensation of phosphoenolpyruvic acid with A-acetyl-D-mannosamine (NAM) catalysed by the biosynthetic enzyme NANA synthase. Owing to the labile nature of phosphoenolpyruvate, the use of this reaction in the synthesis of NANA has been limited to whole-cell systems where this substance can be generated biosynthetically in situ Most recently, the NANA synthase reaction forms the basis of fermentation processes for total biosynthesis of NANA. ... 

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. 

Once the phosphate ester is hydrolysed, there is an immediate rapid tautomerism to the keto form, which becomes the driving force for the metabolic transformation of phosphoenolpyruvic acid into pyruvic acid, and explains the large negative free energy change in the transformation. This energy release is coupled to ATP formation (see Box 7.25). 

Another enzyme with a function very similar to that of aconitase is enolase, which contains magnesium ion (48) and catalyzes the interconversion of phospho-glyceric acid and phosphoenolpyruvic acid. The magnesium can be replaced by... 

Phosphoenolpyruvic acid monopotassium salt (KPEP) [4265-07-0] M 206.1. It is purified via the monocyclohexylamine salt (see next entry). The salt (534mg) in H2O (10ml) is added to Dowex 50 H form (x 4 2 X)-400 mesh, 2ml, H2O washed) and stirred gently for 30min and filtered. The resin is washed with H2O (6ml) and the combined solns are adjusted to pH 7.4 with 3N KOH ( 1.4ml) and the volume adjusted to 18.4ml with H2O to give a soln of O.IM KPEP which can be lyophilised to a pure powder and is very good for enzyme work. It has been recrystd from MeOH-Et2O. It has pKa values of 3.4 and 6.35 in H2O. [Clark and Kirby Biochemical Preparations 11 103 1966 Wold and Ballou JBC 227 301 1957 Cherbuliez and Rabinowitz HCA 39 1461 1956]. 

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)... 

Inhibits enol-pyruvate transferase, which catalyses the incorporation of phosphoenolpyruvic acid (PEP) into uridine diphospho-N-acetylglucoamine (UDPNAG), a precursor involved in the formation of bacterial cell walls. 

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). 

The tenth reaction of the series removes the elements of water from the phosphogiyceric acid, to yield phosphoenolpyruvic acid ... 

Formation of starting materials for cell wall synthesis begins with two metabolic substances normally found in all life forms N-acetylglucosamine 1-phosphate and the pyrimidine nucleotide uridine triphosphate (UTP) (see Fig. 6-3). Condensation of these two compounds by elimination of pyrophosphate affords uridine-diphospho-N-acetylglucosamine (UDPNAG). Reaction with phosphoenolpyruvic acid (PEP, the activated form of the enol tautomer of pyruvic acid),5 catalyzed by a specific transferase, yields the 3-O-enolic ether. 

New routes to phosphoenolpyruvic acid (PEP) which have been explored involve the dealkylation of both phosphoric and carboxylic acid esters by trimethylsilyl halides, and are summarized in Scheme 2. The immediate precursor to the PEP is the tris(trimethylsilyl) ester (18) initial attempts to obtain this from ethyl bromopyruvate failed because the ester (16) could not be further silylated through de-ethylation. However, a synthesis of (18) from... 

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). 

Because shikimic acid does not enter into mammalian metabolism, its synthesis and use are clear targets at which to aim selective toxicity. In bacteria, shikimic acid arises by cyclization of the carbohydrate 3-deoxy-2-oxo-D- mAzVzoheptulosonic acid 7-phosphate, which is formed by the condensation of erythrose 4-phosphate and phosphoenolpyruvic acid. Shikimic acid undergoes biosynthesis to chorismic acid (4.55) which is the enolpyruvic ether of raw5-3,4-dihydroxy cyclohexa-1,5-diene-1-carboxylic acid. As its name indicates, this acid sits at a metabolic fork, the branches of which lead to prephenic acid, to phenylalanine (and hence to tyrosine), to anthranilic acid (and hence tryptophan), to ubiquinone, vitamin K, and/ -aminobenzoic acid (and hence folic acid). 

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