Structure Hemoglobin Tetramer of 2 2 Each subunit binds one heme Oxygen transporter in RBCs Myoglobin Monomer with one heme Oxygen reservoir in muscle Heme Fe 2+ bound to center of protoporphyrin IX Structural Changes To Hemo- globin From Oxygen Binding Two forms from movement of dimers within tetramer Deoxy or tense (T) has low oxygen affinity Oxy or relaxed (R) has high oxygen affinity Binding oxygen to one subunit converts tetramer to R form Cooperative Binding Of Oxygen To Hemoglobin Increasing affinity for oxygen atoms as more subunits of tetramer occupied Binding of Oxygen to Hemoglobin Versus Myoglobin Hemoglobin: multiple cooperative binding sites gives sharp difference in saturation between lungs and tissues Myoglobin: monomer with one binding site; high affinity for oxygen released from hemoglobin in muscle Allosteric Effectors Of Oxygen Binding To Hemoglobin Influence ease of transition between deoxy and oxy forms pH CO 2 2,3-bisphosphoglycerate Effect Of pH Lowering pH promotes release of oxygen Protonation stabilizes deoxy form Lower pH in tissue capillaries than lungs Bohr effect Effect Of CO 2 Promotes release of oxygen CO 2 + H 2 O HCO H + Hb-NH 2 + CO 2 Hb-NH-COO - + H + Carbonic anhydrase reaction lowers pH Carbamate formation stabilizes deoxy form Higher CO 2 in tissue capillaries than lungs Effect Of 2,3-bisphosphoglycerate Normally present in RBCs Promotes release of oxygen by stabilizing deoxy form Adaptation to low oxygen by increasing 2,3-BPG Types Of Hemoglobin Tetramers composed of two -like and two -like subunits Specific developmental expression of subunits HbF has higher affinity for oxygen Hemoglobin A 1c Nonenzymatic addition of glucose to free uncharged amine HbA 1c levels higher in diabetics Sickle-Cell Anemia Amino acid substitution (hydrophobic) in subunit HbS disease (sickle-cell anemia) Aggregates of HbS, deformed RBCs, anoxia, hemolytic anemia (homozygotes) Treatment with hydroxyurea Selective advantage of heterozygotes HbC disease less severe Thalassemias Decreased levels or absence of or subunit -thalassemia: reduced HbA, HbA 2, and HbF -thalassemia: reduced HbA