The 2, 3 diphosphoglycerate (2, 3 DPG) is a compound derived from an intermediate product of glycolysis; it concentrates particularly on the erythrocyte level, since the red blood cells - being devoid of mitochondria - exploit the anaerobic lactate metabolism (homolactical fermentation of glucose) to obtain energy.
Hemoglobin is a tetrameric protein, that is, formed by four subunits, two alpha and two beta, each composed of a protein portion (globine) and an EME (prosthetic group that binds oxygen). 2, 3-diphosphoglycerate attaches to Beta chains by compacting them and reducing the affinity of hemoglobin for oxygen.
The binding of 2, 3 DPG to hemoglobin occurs when it is in the deoxygenated form, while it is dissolved in the lung from the binding of hemoglobin to oxygen. In fact when the hemoglobin reaches the tissues the β-chains are the first to give up the oxygen and this loss involves a displacement of the monomers from the center. As the inner hydrophilic cavity opens the DPG enters and binds to the tetramer forming heteropolar bonds between its negatively charged groups, and the lysine and histidine residues of the beta chains, positively charged. The structure thus stabilized can also release the oxygen of the two α chains. In the lungs, however, the reverse process takes place; at high oxygen pressure the α chains are the first to bind it and the DPG is "squeezed" and expelled from the tetramer, allowing an easier Oxygen-Chain β bond.
The 2, 3-bisphosphoglycerate cannot bind to fetal hemoglobin, since this molecule is devoid of the B chains with which the 2.3 DPG draws its link. This explains the greater affinity for the oxygen of the fetal hemoglobin compared to the maternal hemoglobin, a characteristic that allows the fetal blood to extract oxygen from the maternal blood.