Bisphosphoglycerate BPG Stabilizes the T Structure of Hemoglobin

A low Po2 in peripheral tissues promotes the synthesis in erythrocytes of 2,3-bisphosphoglycerate (BPG) from the glycolytic intermediate 1,3-bisphosphoglycerate.

The hemoglobin tetramer binds one molecule of BPG in the central cavity formed by its four subunits. However, the space between the H helices of the P chains lining the cavity is sufficiently wide to accommodate BPG only when hemoglobin is in the T state. BPG forms salt bridges with the terminal amino groups of both P chains via Val NA1 and with Lys EF6 and His H21 (Figure 6-10). BPG therefore stabilizes de-oxygenated (T state) hemoglobin by forming additional salt bridges that must be broken prior to conversion to the R state.

Residue H21 of the Y subunit of fetal hemoglobin (HbF) is Ser rather than His. Since Ser cannot form a salt bridge, BPG binds more weakly to HbF than to HbA. The lower stabilization afforded to the T state by BPG accounts for HbF having a higher affinity for O2 than HbA.

His H21

His H21

•=0 Val NA1

His H21

Figure 6-10. Mode of binding of 2,3-bisphospho-glycerate to human deoxyhemoglobin. BPG interacts with three positively charged groups on each P chain.

(Based on Arnone A: X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhemoglobin. Nature 1972;237:146. Reproduced with permission.)

His H21

Figure 6-10. Mode of binding of 2,3-bisphospho-glycerate to human deoxyhemoglobin. BPG interacts with three positively charged groups on each P chain.

(Based on Arnone A: X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhemoglobin. Nature 1972;237:146. Reproduced with permission.)

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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