Phosphoenolpyruvate synthesis

The increase in glutamate favors transamination of oxaloacetate and limits oxaloacetate availability for phosphoenolpyruvate synthesis. When the [NADH]/[NAD+] ratio is low, malate formation occurs more readily. The cytosolic PEPCK is relatively unaffected by the mitochondrial [NADH]/[NAD+] ratio. Once malate and aspartate are transported to the cytosol and they are reconverted to oxaloacetate, cytosolic PEPCK can convert it to phosphoenolpyruvate. 

Evans HJ and Wood HG (1968) Phosphoenolpyruvate synthesis from pyruvate. Fed Proc, Abstr 52nd Annu Meet Atlantic City, New Jersey, April 15-20,1968, 2089 Pass S (1987) Superoxide dismutase human efficacy trials for heart attack indication. D-M-Enzyme Rep 6 2... 

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. 

Pyruvate kinase (PK) is one of the three postulated rate-controlling enzymes of glycolysis. The high-energy phosphate of phosphoenolpyruvate is transferred to ADP by this enzyme, which requires for its activity both monovalent and divalent cations. Enolpyruvate formed in this reaction is converted spontaneously to the keto form of pyruvate with the synthesis of one ATP molecule. PK has four isozymes in mammals M, M2, L, and R. The M2 type, which is considered to be the prototype, is the only form detected in early fetal tissues and is expressed in many adult tissues. This form is progressively replaced by the M( type in the skeletal muscle, heart, and brain by the L type in the liver and by the R type in red blood cells during development or differentiation (M26). The M, and M2 isozymes display Michaelis-Menten kinetics with respect to phosphoenolpyruvate. The Mj isozyme is not affected by fructose-1,6-diphosphate (F-1,6-DP) and the M2 is al-losterically activated by this compound. Type L and R exhibit cooperatively in... 

The Jirst indirect route in glucose synthesis involves the formation of phosphoenolpyruvate from pyruvate without the intervention of pyruvate kinase. This route is catalyzed by two enzymes. At first, pyruvate is converted into oxaloacetate. This reaction occurs in the mitochondria as the pyruvate molecules enter them, and is catalyzed by pyruvate carboxylase according to the scheme... 

Bio-Research Products Inc., was founded in 1975, and specialized in the isolation, purification and characterization of enzymes and proteins. The company is well known for its production of wheat germ phosphoenolpyruvate carboxylase (PEPC). Currently, it is involved in finished goods and raw material production, through a biomedical contract. Bio-Research Products runs custom services on enzymes, proteins production, diagnostic assays, and other goods for industry, governments, or academia. Bio-Research Products, Inc. also markets a number of enzymes and associated products, and carries out custom synthesis projects. 

Figure 5.5 The coupled reaction in which ATP supplies the phosphoryl group for glucose-6-phosphate synthesis in contrast, phosphoenolpyruvate has a phosphoryl-transfer potential sufficiently elevated to enable it to donate its phosphoryl group to ADP, generating ATP.

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. ... 

The product phosphoenolpyruvate is able to donate its phosphate group directly to ADP, resulting in ATP synthesis. 

OVERSATURATION OXALOACETATE DECARBOXYLASE Oxaloacetate, synthesis in gluconeogenesis, PYRUVATE CARBOXYLASE PHOSPHOENOLPYRUVATE CARBOXYKI-NASE (PYROPHOSPHATE)... 

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. 

The glucocorticoids have important dose-related effects on carbohydrate, protein, and fat metabolism. The same effects are responsible for some of the serious adverse effects associated with their use in therapeutic doses. Glucocorticoids stimulate and are required for gluconeogenesis and glycogen synthesis in the fasting state. They stimulate phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and glycogen synthase and the release of amino acids in the course of muscle catabolism. 

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 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). 

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]. 

Uptake of Ca2+ into cells, or release of this ion from intracellular stores, is a major regulatory mechanism in many if not all cells (see Section E). Mn2+ activates phosphoenolpyruvate carboxykinase (Eq. 13-46) and maybe a regulator of gluconeogenesis.142 Iron controls the synthesis of ferritin and of transferrin receptors137 (Chapter 16). The specific metal ions present in many biological macromolecules are likely to participate in additional regulatory processes. 

The reversible reaction of phosphoenolpyruvate (PEP) with shikimate 3-phosphate is a step in the synthesis of the aromatic amino acids (see Fig. 25-1). The chemical mechanism indicated... 

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. 

Alkaline pyrophosphatase dependent on Mg2+ was found in every sample examined from a broad spectrum of the plant kingdom (SI). Plants which fix C02 by the dicarboxylic acid pathway have characteristic high levels of alkaline pyrophosphatase in their chloroplasts presumably this performs the rather specific function of driving the synthesis of phosphoenolpyruvate, the immediate precursor of C02 fixation (32). Biosynthesis of the maize chloroplast enzyme is controlled by light acting through the phytochrome system (S3). Pyrophosphatase from spinach chloroplasts has been partially purified (34, 35). 

Fosfomycin trometamol, a stable salt of fosfomycin (phosphonomycin), inhibits a very early stage of bacterial cell wall synthesis (Figure 43-5). An analog of phosphoenolpyruvate, it is structurally unrelated to any other antimicrobial agent. It inhibits the cytoplasmic enzyme enolpyruvate transferase by covalently binding to the cysteine residue of the active site and blocking the addition of phosphoenolpyruvate to UDP-V-acetylglucosamine. This reaction is the first step in the... 

Glycolysis provides the main source of ATP in Trypanosoma brucei, E histolytica, and G lamblia, which possess pyruvate kinase as well as a pyruvate phosphate dikinase for converting phosphoenolpyruvate (PEP) to pyruvate and generating ATP. Pyruvate phosphate dikinase is not a homolog of pyruvate kinase but is closely related to PEP synthase from bacteria. The enzyme catalyzes conversion of PEP to pyruvate accompanied by the synthesis of ATP from AMP and pyrophosphate. Genes encoding the enzyme have been isolated from E histolytica and G lamblia and have demonstrated considerable structural divergences. No specific inhibitor of this enzyme has yet been identified. 

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