Hemoglobin & Myoglobin

  1. function of hemoglobin
    picks up oxygen in the lungs (high oxygen partial pressure/concentration) & delivers it to tissues (low oxygen partial pressure/concentration)
  2. function of arteries
    carries oxygenated blood to tissues (for the most part)
  3. function of veins
    carries deoxygenated blood (for the most part)
  4. Why have we evolved an elaborate oxygen transport system?
    Oxygen is insoluble & cannot dissolve in the bloodstream at high concentrations, thus they need to be bound to a transport protein such as hemoglobin
  5. 3D shapes of hemoglobin & myoglobin
    • Hemoglobin: tetramer (4 subunits, quaternary interaction).
    • Myoglobin: monomer (1 subunit).

    (See slide #3)
  6. A subunit (for both hemoglobin & myoglobin) has __ alpha helices & can bind __ oxygen molecule(s)
    8; 1

    (Hemoglobin has 4 subunits so in total it binds 4 oxygen molecules)
  7. function of myoglobin
    used by muscle cells to transport oxygen to mitochondria
  8. functional groups of a prosthetic heme group
    • methyl (CH3): 4 total.
    • vinyl (has =CH2): 2 total.
    • pyrrole ring (N pentagon): 4 total.
    • propionate (has COOH): 2 total.

  9. Where do coordinate covalent bonds occur on a hemoglobin?
    Coordinate covalent bonds include both pure & polar covalent bonds: Within the prosthetic heme group, there is C-C, N-C, & N-Fe. The N from the proximal Histidine binding to Fe is also considered a coordinate covalent bond.

    (See slide #5)
  10. Where do favorable electrostatic interactions occur on a hemoglobin?
    Oxygen binding to Fe

    (See slide #5)
  11. Where do hydrogen bonds occur on a hemoglobin?
    NH from a distal Histidine binding to the oxygen molecule that is bound to Fe

    (See slide #5)
  12. The __ state occurs in veins
    T (deoxygenated)

    (See slide #3)
  13. The __ state occurs in arteries
    R (oxygenated)

    (See slide #3)
  14. In the __ state, there are 5 coordination contacts to the iron ion
    T (deoxygenated)

    (See slide #6)
  15. In the __ state, there are 6 coordination contacts to the iron ion
    R (oxygenated).

    The oxygen creates the 6th coordination contact.

    (See slide #6)
  16. In the __ state, the iron ion is in a bulged conformation
    T (deoxygenated)

    (See slide #6)
  17. In the __ state, the iron ion is in a NON-bulged conformation
    R (oxygenated)

    (See slide #6)
  18. In the __ state, the inter-tetrameric cavity widens
    T (deoxygenated)

    (See slide #3)
  19. In the __ state, the inter-tetrameric cavity narrows/constricts
    R (oxygenated)

    (See slide #3)
  20. In the __ state, hemoglobin is bound to 2,3-BPG
    T (deoxygenated)
  21. In the __ state, hemoglobin is NOT bound to 2,3-BPG
    R (oxygenated)
  22. subunits of hemoglobin
    4 subunits: alpha1, beta1, alpha2, beta2
  23. Why is hemoglobin binding to oxygen considered positive cooperativity?
    It is multimeric (many subunits) so one subunit influences other subunits to bind to the ligand. Oxygen release also involves cooperativity.
  24. Myoglobin has a __ curve
    hyperbolic - indicative of a single subunit. This shows a strong O2 binding state in both tissues & lungs. Myoglobin will hold onto most of the oxygen.

    (See slide #7)
  25. Hemoglobin has a __ curve
    sigmoidal (s-shaped) - indicative of multiple subunits. This shows a weak binding state in tissues & a strong binding state in lungs

    (See slide #7)
  26. At a normal temp, __ degrees Celcius, the pH would be __ & there would be __ BPG
    37; high (7.40); low (4-5mM)
  27. At a higher temp, __ degrees Celcius, the pH would be __ & there would be __ BPG
    >37; low; higher (8mM)
  28. How is CO2 generated from our bodies?
    One common route is from glucose catabolism (or oxidative breakdown in glycolysis), in which Glucose produces Pyruvate which then produces Acetyl CoA + CO2

  29. A right-shifted sigmoidal curve indicates __ while a left-shifted sigmoidal curve indicates __
    Right: oxygen releasing faster (lower affinity to oxygen), lower pH (7.2), increase in BPG (8mM), increase in temp (>37 degrees)

    Left: oxygen releasing slower (higher affinity to oxygen), higher pH (7.4), decrease in BPG (5mM), normal temp (37 degrees)

    (See slide #8, 12, & 13)
  30. How is CO2 removed? (3 molecular strategies)
    • 1. Major: enzyme catalyzing reaction involving Carbonic Anhydrase
    • 2. Minor: hemoglobin amino terminal carbamation
    • 3. Least prevalent: Dissolving in blood
  31. reactants & products of a carbonic anhydrase enzyme catalyzing reaction
    • Reactants: H2O(l) & CO2(g)
    • Products: H+(aq) protons & HCO3-(aq) bicarbonate

  32. Protons bind to hemoglobin stabilizing __ state, which allows __ oxygen release
    T; faster (Acidified conditions causes hemoglobin to release O2 faster)
  33. reactants & products of an amino terminal carbamation reaction
    • Reactants: R-NH2 (R=side chain of an amino acid) & CO2.
    • Products: Carbamate (1 H is replaced with CO2) & H+.

  34. Both CO2 major & minor removal strategies lead to the production of __ which __ blood pH
    protons (H+); lower
  35. 2 major ways the T (tense) state of hemoglobin is stabilized
    • 1. salt bridge formation
    • 2. BPG binding
  36. function of salt bridges in hemoglobin
    helps hemoglobin transition from an R (relaxed, oxygenated) to a T (tense, deoxygenated) state. makes the T state stabilized
  37. How is 2,3-BPG produced?
    1,3-BPG mutase isomerizes 1,3-BPG & turns it into 2,3-BPG. (This occurs during glucose breakdown.)

    (See slide #11. Note: MUST KNOW HOW TO DRAW 1,3-BPG & 2,3-BPG)
  38. The binding of the first 3 O2 molecules to hemoglobin is __ & the binding of the last O2 molecule is __
    sequential; concerted.

    A sequential model allows for the subsequent conformation change to each subunit in a multimeric protein. In a concerted model, a substantial conformational change has already occurred to the protein (minimal conformational change). A concerted transition will have the highest affinity to O2
  39. When 2,3-BPG binds to hemoglobin, is it a hydrogen bond donor or acceptor?
Card Set
Hemoglobin & Myoglobin
hemoglobin, myoglobin