The affinity of hemoglobin for oxygen.

The delivery of oxygen to the cell depends in good measure upon the affinity with which hemoglobin binds oxygen or releases it from erythrocytes for use by the other cells of the body. The release of oxygen by normal human hemoglobin A, over a range of partial pressures of oxygen, may be represented graphically by the familiar, sigmoid-shaped, oxygen dis-sociation curve. Numerically, the affinity with which hemoglobin binds oxygen may be expressed by the T50 (P50) value which is defined as the partial pressure of oxygen at which 50% of the hemoglobin is saturated with oxygen at a temperature of 37 C and pH of 7.40. If the affinity with which hemo-globin binds oxygen is increased, the oxygen dissociation curve is shifted to the left and the T50 value is decreased from the normal value of 26 to 27 mm Hg Po2. If the affinity with which hemoglobin binds oxygen is decreased , the T50 value is increased. In the past, little physiologic significance was attached to variations in the normal position of the oxygen dissociation curve. Within the last several years, however, renewed attention has been paid to mechanisms whereby alterations in the release of oxygen to the tissues from hemoglobin might enhance the organism's responses to hypoxia. This interest was heightened by the discovery that certain intracellular organic phosphate compounds, namely, adenosine triphosphate (ATP) and, particularly, 2,3 diphosphoglycerate (DPG) exert profound effects upon the release of oxygen from hemoglobin. On oxygenation and deoxygenation the hemoglobin molecule undergoes conforma-tional changes which are associated with binding of certain ligands whereby the combination of one ligand at a particular binding site of hemoglobin further facilitates the binding of other ligands at distant binding sites. Heme-heme interaction and the hemoglobin binding of protons with its reciprocal effects on oxygen binding are examples of these al-losteric effects. Carbon dioxide and certain salts also exhibit heterotropic, allosteric interactions with oxygen which can be demonstrated in dilute solutions of purified hemoglobin. These nonspecific effects depend upon the tetrameric form of a hemoglobin composed of dissimilar hemoglobin chains. In contrast to the myoglobin molecule, there must be more than one binding site on the hemo-globin molecule. In addition, there is evidence to suggest that protons, carbon dioxide, and certain salts bind more firmly to deoxyhemo-globin than to oxyhemoglobin. DPG acts similarly to these ligands in dilute solutions of hemoglobin. Just as is the case with salts, …