1.3 Bisphosphoglycerate

FIGURE 15.36 The structure, in ionic form, of BPG or 2,3-bisphosphoglycerate, an important allosteric effector for hemoglobin. 

A different mechanism operates in the wheat germ enzyme. 2,3-Bisphosphoglycerate is not a cofactor. Instead, the enzyme carries out intra-molecular phosphoryl group transfer (Figure 19.25). The C-3 phosphate is transferred to an active-site residue and then to the C-2 position of the original substrate molecule to form the product, 2-phosphoglycerate. 

A low PO2 in peripheral tissues promotes the synthesis in erythrocytes of 2,3-bisphosphoglycerate (BPG) from the glycolytic intermediate 1,3-bisphosphoglycerate. 

Figure6-10. Mode of binding of 2,3-bisphosphoglycerate to human deoxyhemoglobin. BPG interacts with three positively charged groups on each p chain.

Bisphosphoglycerate (BPG) in the central cavity of deoxyHb forms salt bonds with the (3 subunits that stabilize deoxyHb. On oxygenation, the central cavity contracts, BPG is extruded, and the quaternary structure loosens. 

In erythrocytes, the first site in glycolysis for generation of ATP may be bypassed, leading to the formation of 2,3-bisphosphoglycerate, which is important in decreasing the affinity of hemoglobin for Oj. 

Production of 2,3-bisphosphoglycerate, by reactions closely associated with glycolysis, is important in regulating the ability of Hb to transport oxygen. 

J4. Joulin, V., Peduzzi, J., Remeo, P.-H., Rosa, R., Valentin, C., Dubart, A., Lapeyre, B Blouquit, Y., Garel, M.-C., Goossens, M., Rosa, J., and Cohen-Solal, M., Molecular cloning and sequence of the human erythrocyte 2,3-bisphosphoglycerate mutase cDNA Revised amino acid sequence. EM BO J. 5, 2275-2283 (1986). 

P. J. Mulquiney and P. W. Kuchel, Model of 2,3 bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations Computer simulation and metabolic control analysis. Biochem. J. 342 (3), 597 604 (1999). 

Fig. 3. Binding site of 2,3-bisphosphoglycerate (DPG) between the two /3 chains in human deoxyhemoglobin. On transition to the oxy struaure, the a-amino groups move apart and the EF segments close up, so that the complementarity of the binding site to DPG is lost (103).

We next turn to the effect of adding D-2,3-bisphosphoglycerate (BPG, previously known as DPG) and inositol hexaphosphate (IHP). 

BI Binding isothenn BP Binding polynomial BPG D-2,3-bisphosphoglycerate CPF Canonical partition function FG Functional group GPF Grand partition function IHP Inositol hexaposphate Ihs Left-hand side PF Partition function rhs Right-hand side H( )0 Hydrophobic H( )I Hydrophilic... 

Figure 6.13 The effect of different concentrations of 2,3-bisphosphoglycerate on the oxyhaemoglobin dissociation curve. The increase in the concentration of BPG from 4 to 5 mmol/L results in an increase in the amount of oxygen released in the capillaries by more than 20%. The concentration of BPG decreases on storage of erythrocytes, so that cells from the blood bank have a higher affinity for oxygen and hence discharge less oxygen in the tissue.

Box 6.1 2,3-Bisphosphoglycerate and the dissociation of oxygen from oxyhaemoglobin in patients and athletes... 

The concentration in the erythrocytes of 2,3-bisphosphoglycerate that influences the dissociation curve of oxyhaemoglobin (Chapter 6). 

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