Hemoglobin 2,3-bisphosphoglycerate binding

Hemoglobin also binds H+ and C02, resulting in the formation of ion pairs that stabilize the T state and lessen the protein s affinity for 02 (the Bohr effect). Oxygen binding to hemoglobin is also modulated by 2,3-bisphosphoglycerate, which binds to and stabilizes the T state. 

H+, C02 and 2,3-bisphosphoglycerate are allosteric effectors, promoting the release of 02 from hemoglobin. H+ and C02 bind to different parts of the polypeptide chains, while 2,3-bisphosphoglycerate binds in the central cavity between the four subunits. 

Bisphosphoglycerate binding controls the affinity of hemoglobin for oxygen. It is synthesized in the erythrocyte from an intermediate in a major metabolic pathway and defects in this pathway sometimes produce important... 

One molecule of 2,3-bisphosphoglycerate binds to one molecule of hemoglobin in a central cavity of the hemoglobin molecule, is the interaction between BPG and hemoglobin stronger or weaker than it would be if BPG bound to the surface of the protein instead Explain your answer. 

Some patients with erythrocytosis (excess RBCs) have a mutation that converts a lysine to alanine at amino acid 82 in the 3 subunit of hemoglobin. This particular lysine normally protrudes into the central cavity of deoxyhemoglobin, where it participates in binding 2,3-bisphosphoglycerate (BPG). 

Hemoglobin F (HbF) which consists of two a-chains and two y-chains (a2y2) is present in the fetus. HbF binds 2,3-bisphosphoglycerate less strongly than adult hemoglobin (HbA) and thus has a higher affinity for 02 which promotes the transfer of Oz from the maternal to the fetal circulation. 

In addition, allosteric enzymes may be controlled by effector molecules (activators and inhibitors) that bind to the enzyme at a site other than the active site (either on the same subunit or on a different subunit), thereby causing a change in the conformation of the active site which alters the rate of enzyme activity (cf. the binding of C02, H+ and 2,3-bisphosphoglycerate to hemoglobin see Topic B4). An allosteric activator increases the rate of enzyme activity, while an allosteric inhibitor decreases the activity of the enzyme. 

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 ... 

Figure 2-13. Oxygen saturation curves for myoglobin and adult hemoglobin (HbA). Myoglobin has a hyperbolic saturation curve. HbA has a sigmoidal curve. The HbA curve shifts to the right at lower pH, with higher concentrations of 2,3-bisphosphoglycerate (BPG), or as C02 binds in the tissues. Thus, 02 is released more readily. P50 ( ) is the partial pressure of 02 at which HbA is half-saturated with 02.

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