1. Structure Hemoglobin –Tetramer of  2  2 –Each subunit binds one heme –Oxygen transporter in RBCs Myoglobin –Monomer with one heme –Oxygen reservoir in muscle

2. Heme Fe 2+ bound to center of protoporphyrin IX

3. 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

4. Cooperative Binding Of Oxygen To Hemoglobin Increasing affinity for oxygen atoms as more subunits of tetramer occupied

5. 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

6. Allosteric Effectors Of Oxygen Binding To Hemoglobin Influence ease of transition between deoxy and oxy forms pH CO 2 2,3-bisphosphoglycerate

7. Effect Of pH –Lowering pH promotes release of oxygen –Protonation stabilizes deoxy form Lower pH in tissue capillaries than lungs Bohr effect

8. Effect Of CO 2 Promotes release of oxygen CO 2 + H 2 O ↔ HCO 3 - + 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

9. 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

10. Types Of Hemoglobin Tetramers composed of two  -like and two  -like subunits Specific developmental expression of subunits HbF has higher affinity for oxygen

11. Hemoglobin A 1c Nonenzymatic addition of glucose to free uncharged amine HbA 1c levels higher in diabetics

12. 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

13. Thalassemias Decreased levels or absence of  or  subunit  -thalassemia: reduced HbA, HbA 2, and HbF  -thalassemia: reduced HbA