tailieunhanh - Chapter 099. Disorders of Hemoglobin (Part 2)

Hemoglobin-oxygen dissociation curve. The hemoglobin tetramer can bind up to four molecules of oxygen in the iron-containing sites of the heme molecules. As oxygen is bound, 2,3-BPG and CO2 are expelled. Salt bridges are broken, and each of the globin molecules changes its conformation to facilitate oxygen binding. Oxygen release to the tissues is the reverse process, salt bridges being formed and 2,3-BPG and CO2 bound. Deoxyhemoglobin does not bind oxygen efficiently until the cell returns to conditions of higher pH, the most important modulator of O2 affinity (Bohr effect). When acid is produced in the tissues, the dissociation curve. | Chapter 099. Disorders of Hemoglobin Part 2 Figure 99-2 Hemoglobin-oxygen dissociation curve. The hemoglobin tetramer can bind up to four molecules of oxygen in the iron-containing sites of the heme molecules. As oxygen is bound 2 3-BPG and CO2 are expelled. Salt bridges are broken and each of the globin molecules changes its conformation to facilitate oxygen binding. Oxygen release to the tissues is the reverse process salt bridges being formed and 2 3-BPG and CO2 bound. Deoxyhemoglobin does not bind oxygen efficiently until the cell returns to conditions of higher pH the most important modulator of O2 affinity Bohr effect . When acid is produced in the tissues the dissociation curve shifts to the right facilitating oxygen release and CO2 binding. Alkalosis has the opposite effect reducing oxygen delivery. Oxygen affinity is modulated by several factors. The Bohr effect is the ability of hemoglobin to deliver more oxygen to tissues at low pH. It arises from the stabilizing action of protons on deoxyhemoglobin which binds protons more readily than oxyhemoglobin because it is a weaker acid Fig. 99-2 . Thus hemoglobin has a lower oxygen affinity at low pH. The major small molecule that alters oxygen affinity in humans is 2 3-bisphosphoglycerate 2 3-BPG formerly 2 3-DPG which lowers oxygen affinity when bound to hemoglobin. HbA has a reasonably high affinity for 2 3-BPG. HbF does not bind 2 3-BPG so it tends to have a higher oxygen affinity in vivo. Hemoglobin also binds nitric oxide reversibly this interaction may influence vascular tone but its physiologic relevance remains unclear. Proper oxygen transport depends on the tetrameric structure of the proteins the proper arrangement of the charged amino acids and interaction with protons or 2 3-BPG. Developmental Biology of Human Hemoglobins Red cells first appearing at about 6 weeks after conception contain the embryonic hemoglobins Hb Portland Z2Y2 Hb Gower I Z2e2 and Hb Gower II a2e2 . At 10-11 weeks fetal .