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Structure

Structure. Hemoglobin. Tetramer of a 2 b 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.

sebastian-moore
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Structure

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  1. Structure • Hemoglobin • Tetramer of a2b2 • Each subunit binds one heme • Oxygen transporter in RBCs • Myoglobin • Monomer with one heme • Oxygen reservoir in muscle

  2. Heme • Fe2+ bound to center of protoporphyrin IX

  3. Structural Changes To Hemo-globin From Oxygen Binding • Two forms from movement of ab 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 • CO2 • 2,3-bisphosphoglycerate

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

  8. Effect Of CO2 • Promotes release of oxygen • Carbonic anhydrase reaction lowers pH CO2 + H2O ↔ HCO3- + H+ • Carbamate formation stabilizes deoxy form Hb-NH2 + CO2 ↔ Hb-NH-COO- + H+ • Higher CO2 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 a-like and two b-like subunits • Specific developmental expression of subunits • HbF has higher affinity for oxygen

  11. Hemoglobin A1c • Nonenzymatic addition of glucose to free uncharged amine • HbA1c levels higher in diabetics

  12. Sickle-Cell Anemia • Amino acid substitution (hydrophobic) in b 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 a or b subunit • a-thalassemia: reduced HbA, HbA2, and HbF • b-thalassemia: reduced HbA

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