Disease relevance of 2-phosphoglyceric acid

• Salmonella typhimurium strain LT-2 was found to utilize phosphoenolpyruvate, 2-phosphoglycerate, and 3-phosphoglycerate as sole sources of carbon and energy for growth, but Escherichia coli strains did not [1].
• Spectroscopic and kinetic methods have been used to explore the roles of divalent metal ions in the enolase-catalyzed dehydration of 2-phosphoglycerate (2-PGA) [2].
• Degradation of 2-phosphoglycerate by cytotoxin B of Clostridium difficile [3].
• Phosphoenolpyruvate and 2-phosphoglycerate: endogenous energy source(s) for sugar accumulation by starved cells of Streptococcus lactis [4].
• Phosphoglycerate mutase is an essential glycolytic enzyme for Zymomonas mobilis, catalyzing the reversible interconversion of 3-phosphoglycerate and 2-phosphoglycerate [5].

High impact information on 2-phosphoglyceric acid

• Although transformation had no apparent effect on the K0.5 of enolase (26 +/- 4 microM for 2-phosphoglycerate), its specific activity was reduced by about one third [6].
• Glucose could be replaced by intravesicular (but not extravesicular) fructose 1,6-bisphosphate, gluconate 6-phosphate, or 2-phosphoglycerate, but not by other phosphorylated metabolites, in agreement with the allosteric activating effects of these compounds on HPr(Ser) kinase measured in vitro [7].
• Protein phosphorylation in pancreatic islets induced by 3-phosphoglycerate and 2-phosphoglycerate [8].
• Surprisingly, no increase of 2-phosphoglycerate occurs, which suggests that inefficient phosphoglyceromutase activity underlies this perturbation of erythrocyte metabolism and its associated hemolytic process [9].
• The intact 2-phosphoglycerate bound to the active site of the other subunit has been observed in two different orientations [10].

Chemical compound and disease context of 2-phosphoglyceric acid

• The Km values for the Hyphomicrobium X enzyme were: 3-phosphoglyceric acid, 6-0 X 10(-3) M: 2-phosphoglyceric acid, 6-9 X 10(-4) M; 2,3-diphosphoglyceric acid, 8-0 X 10(-6) M; and for the Pseudomonas AMI ENzyme: 3-4 X 10(-3) M, 3-7 X 10(-4) M and 10 X 10(-6) M respectively [11].

Biological context of 2-phosphoglyceric acid

• The B-type cofactor-dependent phosphoglycerate mutase (dPGM-B) catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglycerate in glycolysis and gluconeogenesis pathways using 2,3-bisphosphoglycerate as the cofactor [12].
• Glycolysis and gluconeogenesis are, in part, driven by the interconversion of 3- and 2-phosphoglycerate (3-PG and 2-PG) which is performed by phosphoglycerate mutases (PGAMs) which can be cofactor dependant (dPGAM) or cofactor independent (iPGAM) [13].
• Homologs with high sequence identity were identified in the genomes of the archaea Thermoplasma and Sulfolobus spp. and Thermoproteus tenax, for which the operation of nonphosphorylative ED pathways, involving 2-phosphoglycerate forming glycerate kinases, has been proposed [14].
• The enzyme showed broad substrate specificity, hydrolyzing preferentially 4-nitrophenyl phosphate, O-phosphoamino-acids and 2-phosphoglycerate [15].

Anatomical context of 2-phosphoglyceric acid

• Formation of 2-phosphoglycerate is also observed when isolated mitochondria from rat liver are incubated together with glyceraldehyde and an energy source [16].
• The enzyme beta-enolase (alpha beta and beta beta forms) is present in skeletal and heart muscle and catalyses the glycolysis of 2-phosphoglycerate to phosphoenolpyruvate [17].

Associations of 2-phosphoglyceric acid with other chemical compounds

• These data support the carbanion mechanism for enolase and suggest that the 3-hydroxyl of 2-phosphoglycerate is directly coordinated to Mg2+ prior to being eliminated to give phosphoenolpyruvate [18].
• The pH variation of the kinetic parameters for the methylene analogue of 2-phosphoglycerate suggests that the substrate binds as a dianion and that Mg2+ can bind subsequently only if a metal ligand and the catalytic base are unprotonated [19].
• These encode, in three transcriptional units, (D)-glucarate dehydratase (GlucD), galactarate dehydratase, 5-keto-4-deoxy-(D)-glucarate aldolase, tartronate semialdehyde reductase, a glycerate kinase that generates 2-phosphoglycerate as product, and two hexaric acid transporters [20].
• Cells of Picrophilus torridus, grown on glucose, contained all enzyme activities of a non-phosphorylative Entner-Doudoroff pathway, including glucose dehydrogenase, gluconate dehydratase, 2-keto-3-deoxygluconate aldolase, glyceraldehyde dehydrogenase (GADH), glycerate kinase (2-phosphoglycerate forming), enolase and pyruvate kinase [21].
• The protective effect of monophosphoglycerates could be rationalized with kinetic evidence that 2-phosphoglycerate at high concentrations interacts with the 2,3-bisphosphoglycerate binding site [22].

Gene context of 2-phosphoglyceric acid

• Enolase (EC 4.2.1.11) is an enzyme of the glycolytic pathway catalyzing the dehydratation reaction of 2-phosphoglycerate [23].
• Inhibition of enolase: the crystal structures of enolase-Ca2(+)- 2-phosphoglycerate and enolase-Zn2(+)-phosphoglycolate complexes at 2.2-A resolution [24].
• The optimal pH, stability against heating, and Km for 2-phosphoglycerate of the hybrid enolase were also similar to those of the homodimeric enolases [25].
• Interaction of the C-terminal residues Ala239 and Val240 of PGM (which partially "cap" the 2-phosphoglycerate) with enolase also favors the existence of channeling [26].
• In this communication we report the crystal structure of Plasmodium falciparum triose-phosphate isomerase complexed to the inhibitor 2-phosphoglycerate at 1.1-A resolution [10].

Analytical, diagnostic and therapeutic context of 2-phosphoglyceric acid

• On the basis of inhibition studies and thin-layer chromatography of cell extracts, we suggest that 3- and 2-phosphoglycerate are the principal constituents of the pool [27].
• 2DG phosphate (2DG-P) accumulation in these vesicles was not inhibited, and preaccumulated 2DG-P was not released from them, upon electroporation of fructose 1,6-diphosphate (FDP), gluconate 6-phosphate or 2-phosphoglycerate into the vesicles [28].
• 2. There is a significant fall in the content of ADP, AMP, citrate, long-chain acyl-CoA derivatives and a rise of 3-phosphoglycerate, 2-phosphoglycerate and phosphoenolpyruvate following thyroidectomy [29].

References