Disease relevance of 2,3-Bisphosphoglycerate

• To explain the transient anemia and poikilocytosis seen during infancy in hereditary elliptocytosis (HE), we resealed erythrocyte (RBC) ghosts from affected children or their elliptocytic parents with 2,3-diphosphoglycerate (DPG) (0-8 mM), a compound that dissociates membrane skeletons, then measured ghost mechanical stability in the ektacytometer [1].
• Bacillus stearothermophilus phosphoglycerate mutase (PGM), which interconverts 2- and 3-phosphoglyceric acid (PGA), does not require 2,3-diphosphoglyceric acid for activity [2].
• In 2,3-diphosphoglycerate mutase deficiency, 2,3-diphosphoglycerate is greatly reduced and asymptomatic polycythemia is noted [3].
• Effects of methylprednisolone on P50, 2,3 diphosphoglycerate and arteriovenous oxygen difference in acute myocardial infarction [4].
• Physiologic features of hemolysis axxociated with altered cation and 2,3-diphosphoglycerate content [5].

Psychiatry related information on 2,3-Bisphosphoglycerate

• 31P NMR relaxation time studies of 2,3-diphosphoglycerate in solution and intact erythrocytes [6].

High impact information on 2,3-Bisphosphoglycerate

• 2,3-Diphosphoglycerate in erythrocytes of chick embryos [7].
• 2,3-diphosphoglycerate: a physiological inhibitor of platelet aggregation [8].
• The purpose of this study was to investigate the effect of infusion of 400 mL of red blood cells (RBCs) on 10-km track race time, submaximal heart rate, hematocrit, 2,3-diphosphoglycerate, and partial pressure of oxygen at 50% hemoglobin saturation [9].
• We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V gamma 9/V delta T cells ex vivo, antagonizes the same cell population after repetitive activation [10].
• The competitive PLD inhibitor 2,3-diphosphoglycerate (2,3-DPG) produced concentration-dependent inhibition of PLD activity stimulated by either M. tuberculosis (-78 +/- 8%) or OZ (-73 +/- 6%) [11].

Chemical compound and disease context of 2,3-Bisphosphoglycerate

• The ammonium chloride acidosis caused a small decrease in red blood cell 2,3-diphosphoglycerate levels but no alteration in oxygen pressure at 50% saturation at pH 7.4, sickling, or adverse effects [12].
• A red cell additive solution (AS-005) containing ascorbate-2-phosphate (AsP) to maintain 2,3-diphosphoglycerate, plus adenine, phosphate, and mannitol to retain viability and reduce hemolysis, was evaluated by human clinical trials [13].
• Structural studies on a 2,3-diphosphoglycerate independent phosphoglycerate mutase from Bacillus stearothermophilus [14].
• There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance [15].
• In this communication, we describe a method for analysis of glucose metabolites in erythrocytes from healthy donors during storage in blood bags, and from patients with thalassemia, with special respect to intracellular 2,3 bisphosphoglycerate, lactate and ATP/ADP [16].

Biological context of 2,3-Bisphosphoglycerate

• Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions [17].
• We conclude that the nonenzymatic glycosylation of hemoglobin is influenced by factors other than glucose, including oxygen tension and 2,3-diphosphoglycerate levels [18].
• From osmotic fragility, plasma trapping, erythrocyte ATP and 2,3-diphosphoglycerate (DPG), and serum phosphorus, calcium, and magnesium measurements it seems unlikely that either spheric transformation or sol-gel transformation of the membrane is causing the increased erythrocyte rigidity [19].
• Sherpas living permanently at 4000 m above sea level do not have increased hematological parameters (i.e., red cell number, hematocrit, hemoglobin content, and 2,3-diphosphoglycerate/hemoglobin ratio) and have a higher affinity of blood for oxygen as compared with acclimatized Caucasians [20].
• In such cells the PGK step presumably was inoperative due to total lack of substrate; 2,3-diphosphoglycerate (2,3-DPG) then became the sole substrate source for remaining steps in glycolysis [21].

Anatomical context of 2,3-Bisphosphoglycerate

• The reticulocytes increased from 1.4 +/- 1.8 to 3.1 +/- 2.9% (P less than 0.05) and the 2,3-diphosphoglycerate decreased from 4.4 +/- 1.1 to 2.8 +/- 1.2 mumol/g hemoglobin (P less than 0.005) [22].
• Treatment with 2,3-diphosphoglycerate resulted in membranes with decreased deformability and decreased stability, whereas treatment with diamide produced decreased deformability but increased stability [23].
• The initial concentration of 2,3-diphosphoglycerate in sickle cell blood was about 30% higher, but it was depleted much faster during incubation than that in normal blood [24].
• Red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin in patients with thyroid disorders [25].
• The oxygen affinity of hemoglobin in K562 cells induced by hemin and the relationship between levels of 2,3-diphosphoglycerate (2,3-DPG) and hemoglobin have been investigated [26].

Associations of 2,3-Bisphosphoglycerate with other chemical compounds

• Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings [17].
• Intracellular phosphate concentrations were markedly pH dependent and a model is presented whereby hypoxanthine uptake and release are controlled by intracellular concentrations of inorganic phosphate and 2,3-bisphosphoglycerate [27].
• Cystamine did not affect the intracellular pH nor the 2,3-diphosphoglycerate level [28].
• The erythrocyte 2,3-diphosphoglycerate content was markedly reduced and the cell chloride content was consequently increased [29].
• Intracellular pH and 2,3-diphosphoglycerate concentration in sickle cell amenia and normal human blood samples were measured by means of phosphorus-31 nuclear magnetic resonance spectroscopy [24].

Gene context of 2,3-Bisphosphoglycerate

• The human erythrocyte 2,3-bisphosphoglycerate mutase (BPGM) is a multifunctional enzyme which controls the metabolism of 2,3-diphosphoglycerate, the main allosteric effector of haemoglobin [30].
• This is the first report of the amino acid sequence of a 2,3-bisphosphoglycerate cofactor-independent phosphoglycerate mutase, which consists of 559 amino acids and is twice the molecular size of the mammalian cofactor-dependent enzyme subunit [31].
• Phosphoglycerate mutase is a dimer, partially independent of 2,3-bisphosphoglycerate, and has a high specific activity [32].
• Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas [33].
• Human B-type 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (dPGM-B) has been cloned, overexpressed and purified, with a yield of 30% of the total protein [34].

Analytical, diagnostic and therapeutic context of 2,3-Bisphosphoglycerate

• But these haemoglobins cannot be used as a blood substitute because (1) the oxygen affinity in the absence of 2,3-bisphosphoglycerate is too high to allow unloading of enough oxygen in the tissues, and (2) they dissociate into alpha beta dimers that are cleared rapidly by renal filtration, which can result in long-term kidney damage [35].
• A new process allows microencapsulation of purified human hemoglobin and 2,3-diphosphoglycerate to form neohemocytes [36].
• Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis [37].
• Pure recombinant hemoglobin S was shown to be identical to natural sickle hemoglobin in its ultraviolet and visible absorption bands and by gel electrophoresis, isoelectric focusing, amino acid analysis, mass spectrometry, partial N-terminal sequencing, and functional properties (P50, cooperativity, and response to 2,3-bisphosphoglycerate) [38].
• X-ray crystallography of normal human hemoglobin has shown that the beta 2 residue is normally part of the binding site for 2,3-diphosphoglycerate [39].

References