1 / 13

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
Download Presentation

Structure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related