2,3-Diphosphoglycerate, hemoglobin

Fig. 2. Reaction of diphosphoglycerate (2,3-DPG) and deoxyhemoglobin. The molecule fits into the central cavity of hemoglobin and forms salt bridges with valine NA(I)p, histidines NA2(2)p, H2I(I43)p, and lysine EF6(82)p. A, E, and E correspond to specific hemoglobin hehces and NA is the sequence...

The 3D structure of the 2,3-diphosphoglycerate (DPG) complex of hemoglobin (Hb) served to derive simple aromatic dialdehydes that mimic the function of DPG as an allosteric modulator of the oxygen affinity of Hb. Some of the resulting compounds were as active and even more active than DPG, the natural ligand [1-3]. 

Diphosphoglycerate A compound in red blood cells that affects oxygen binding to and release from hemoglobin. 

Hemoglobin s dioxygen binding is regulated by local concentrations of H+ (known as the Bohr effect), CO2 concentration, and organic phosphates such as diphosphoglycerate (DPG), whose structure is shown in Figure 4.2.17... 

Figure 10.11 Binding of 2,3-diphosphoglycerate (DPG) between the f3 chains in the central cavity of human hemoglobin. [From A. Amone and M. F. Perutz, Nature, Land. 249, 34 (1974).]...

Scaloni A, Ferranti P, De Simone G et al (1999) Probing the reactivity of nucleophile residues in human 2,3-diphosphoglycerate/deoxy-hemoglobin complex by aspecific chemical modifications. FEBS Lett 452 190-194... 

Figure 7.8 Equilibria among the R and T forms of hemoglobins ar-chains are represented by circles, /3-chains by squares. The clamps represent electrostatic interactions. >-< represents 2,3-diphosphoglycerate. a, b, c and d represent electrostatic linkages that are broken or formed in the processes of interconversion between the reversible tight to relaxed conformation.

Diphosphoglycerate (2,3-DPG) is an important mediator of hemoglobin physiology (see Chapter 7). It is synthesized from 1,3-diphosphoglycerate. The... 

The compound 2,3-bisphosphoglycerate (BPG, also known as 2,3-diphosphoglycerate or DPG) is produced within the red blood cell of many animal species, and acts to modify the oxygen binding affinity of hemoglobin ... 

It is well known that the O2 affinity of vertebrate hemoglobin affects several physiological effectors such as H+, CO2 or 2,3-diphosphoglycerate (2,3-DPG). Particularly, H+... 

Figure 3.13. Diphosphoglycerate (a) and analogs (b-d) designed to optimize interactions bound in schematic model of hemoglobin. Used with permission (169).

B79. Bimn, H. F., Differences in the interaction of 2,3-diphosphoglycerate with certain mammalian hemoglobins. Science 172, 1049-1050 (1971). 

Ascorbic acid appears to be toxic to certain tumor tissues however, it may increase the biological effectiveness of red blood cells by increasing the level of 2,3-diphosphoglycerate (30,31), 2,3-Diphosphoglycerate is essential to maintaining the normal oxygen dissociation curve of hemoglobin. This increase has been shown in vitro (30) and in vivo, in human subjects (31). 

Figure 28-19 Three compounds designed by Beddell and coworkers to mimic the binding of 2.3-diphosphoglycerate (DPG) (2) to hemoglobin.

The clinical manifestations of serum phosphate depletion depend on the length and degree of the deficiency. Moderate hypophosphatemia of 1.5 to 2,4 mg/dL (0.48 to 0.77 mmol/L) is usually not associated with clinical signs and symptoms (unless chronic, when osteomalacia or rickets develops). Plasma concentrations less than 1.5 mg/dL (0.48 mmol/L) may produce clinical manifestations. Because phosphate is necessary for the formation of ATP, glycolysis and cellular function are impaired by low intracellular phosphate concentrations. Muscle wealmess, acute respiratory failure, and decreased cardiac output may occur in phosphate depletion. At very low serum phosphate (<1 mg/dL or <0.32 mmol/L), rhabdomyolysis may occur. Phosphate depletion in erythrocytes decreases erythrocyte 2,3-diphosphoglycerate, which causes tissue hypoxia because of increased affinity of hemoglobin for oxygen. Severe hypophosphatemia (serum phosphate concentration <0.5 mg/dL [<0.16 mmol/L]) may result in hemolysis of the red blood cells. Mental confusion and frank coma also may be secondary to the low ATP and tissue hypoxia. If hypophosphatemia is chronic, impaired mineralization of bone produces rickets in children and osteomalacia in adults. 

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