Enolate anions pyruvate

Phosphoenolpyruvate, a key metabolic intermediate. A compound of central importance in metabolism is the phosphate ester of the enol form of pyruvate, commonly known simply as phosphoenolpyruvate (PEP).249 It is formed in the glycolysis pathway by dehydration of 2-phosphoglycerate (Eq. 13-15) or by decarboxylation of oxaloacetate. Serving as a preformed enol from which a reactive enolate anion can be released for condensation reactions,250 251 PEP... 

Oxaloacetate is also decarboxylated without phosphorylation of the enolate anion formed but with release of free pyruvate. Both pyruvate kinase and PEPCK can act as oxaloacetate decarboxylases.261... 

When pyruvate with a chiral methyl group is carboxylated by pyruvate carboxylase the configuration at C-3 is retained. The carboxyl enters from the 2-si side, the same side from which the proton (marked H ) was removed to form the enolate anion (Eq. 14-12). Comparable stereochemistry has been established for other biotin-dependent enzymes.64 65... 

These enzymes do not catalyze any proton exchange at C-3 of pyruvate or at C-2 of an acyl-CoA unless the biotin is first carboxylated. This suggested that removal of the proton to the biotin oxygen and carboxylation might be synchronous. However, 13C and 2H kinetic isotope effects and studies of 3H exchange66 support the existence of a discrete enolate anion intermediate as shown in Eq. 14-11.165/67 This mechanism is also consistent with the observation that propionyl-CoA... 

Chemical properties appropriate to a compound found at a branch point of metabolism are displayed by chorismic acid. Simply warming the compound in acidic aqueous solution yields a mixture of prephen-ate and para-hydroxybenzoate (corresponding to reactions h and l of Fig. 25-1). Note that the latter reaction is a simple elimination of the enolate anion of pyruvate. As indicated in Fig. 25-1, these reactions correspond to only two of several metabolic reactions of the chorismate ion. In E. coli the formation of phe-nylpyruvate (steps h and i, Fig. 25-1) is catalyzed by a single protein molecule with two distinctly different enzymatic activities chorismate mutase and prephenate dehydratase.34-36 However, in some organisms the enzymes are separate.37 Both of the reactions catalyzed by these enzymes also occur spontaneously upon warming chorismic acid in acidic solution. The chorismate mutase reaction, which is unique in its mechanism,373 is discussed in Box 9-E. Stereochemical studies indicate that the formation of phenylpyruvate in Fig. 25-1, step z, occurs via a... 

On the basis of this structural information, the pathway of the MPS reaction can be outlined as follows (Scheme 27) oxalacetate is incorporated into the active site of MPS in a similar way to that of pyruvate. Lewis acidity of the magnesium promotes decarboxylation to form the enolate anion, which is stabilized by an electron sink provided by the divalent cation. Steric congestion of the peptide backbone allows the 2-pyrone... 

There are countless synthetic examples of the aldol condensation. In one example taken from Massanet s synthesis of eudesmanolides, diketone 134 was converted to the enolate anion with LDA. In a second step, methyl pyruvate was added to give a 98% yield of 135 and 136 in about a 1 1 ratio. 

The simplest mechanism for this step is analogous to that given above for formation of carboxybiotin carboxybiotin initially decarboxylates to give CO2 and a nitrogen anion this anion then removes a proton from the methyl group of pyruvate and the resulting enolate reacts with CO2. 

The role of the metal ion in this reaction is unknown. By analogy with other pyruvate-dependent enzymes, the metal may be used to stabilize the enolate. Alternatively, the role of the metal may be to stabilize the biotin anion by com-plexation to oxygen. 

Thiamine anions add to aldehydes and ketones (e.g., acetaldehyde, carbohydrates, and pyruvic acid). Pyruvic acid adducts decarboxylate with a half-life of 24 hours in water and 3.2 minutes in ethanol, since ethanol cannot stabilize the intermediate zwitterion as well as water. After acidification, acetaldehyde is split off. In the adduct between acetaldehyde and thiamine, the electrophilic carbon atom of the aldehyde undergoes an Umpolung " to a resonance-stabilized enolate carbon atom. The thiazole-bound acetaldehyde then functions as carban-ion in Michael additions under mildly basic conditions. Retro-aldo reactions are observed, when 1,3-thiazolium ions react with the carbonyl groups of carbohy-... 

The anion (147), a synthon of methyl a-lithioacrylate, has been prepared but unfortunately, owing to its chelated structure, it is rather unreactive and viable yields have been obtained only in reactions with primary allylic halides (c/. 3, 112). Sensitive enol pyruvates (149) can be obtained in ca. 30% yield from the corresponding methyl a-hydroxypropionate derivatives (148) by sequential enolate formation, addition of phenylselenenyl bromide, and oxidative elimination using hydrogen peroxide. ... 

Pyruvate-dependent aldolases reversibly catalyze the aldol addition of p)u uvate or analogues to aldehydes yielding y-hydroxy-a-oxoacids (Figure 10.1). They exist as Class I aldolases (i.e., Schiff base/enamine formation) and Class 11 (i.e., metal cofactor and enolate formation) aldolases (Figure 10.2) [45, 46]. Class 11 pyruvate aldolases contain a Mg, Mn, or Co divalent metal cation in octahedral coordination, which stabilizes the nucleophile (i.e., p5U uvate anion) in the active site [45,47]. 

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