Ch 7 Text 2

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Ch 7 Text 2
2014-09-23 19:49:18
Test Two
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  1. ·         Oxygen binding properties can be determined by __, a plot of the __ versus __
    o   The fractional saturation, Y, is what?
    o The concentration of oxygen is measured by __
    • oxygen-binding curve
    • fractional saturation versus the concentration of oxygen

    the fraction of possible binding sites that contain bound oxygen and can range from 0 to 1 (all sites filled)

    partial pressure
  2. ·         Half saturation of the binding sites, referred to as __ is at the relatively low value of __, indicating that oxygen does what?
    o   Myoglobin binding curve: __
    o   Hemoglobin binding curve: __
    • P50 (50% saturated)
    • 2 mm Hg

    binds with high affinity to myoglobin

    curve rises sharply as pO2 increases and then levels off

    resembles an S (sigmoid); oxygen binding for hemoglobin is weaker than that for myoglobin. Inside red cells, hemoglobin interacts with 2,3-bisphosphoglycerate, a molecule that lowers hemoglobin’s oxygen affinity
  3. ·        What does a sigmoid binding curve indicate?

    On the other hand, the unloading of oxygen causes __. This is called __ because __.
    that a protein shows a special binding behavior, which, for hemoglobin, suggest that binding of oxygen at one site increases affinity at other sites

    unloading at others

    • cooperative because the binding sites are not independent of one another
  4. · Physiological significance of the cooperation? ____
    Why can't myoglobin do it?
    The cooperative release of oxygen favors a more complete unloading of oxygen in the tissues

    o Myoglobin binds oxygen too tightly to be used for oxygen transport
  5. ·         Without cooperativity, this could have been improved by the evolution of a __. The most oxygen that could be transported from a region with 100 torr pO2 to one with 200 torr is __. Thus, cooperative binding and release of oxygen by hemoglobin allows __
    noncooperative oxygen carrier with an optimized affinity for oxygen


    10 x as much oxygen to be delivered
  6. ·         Under resting conditions, the oxygen concentration in muscle is approximately __, but during exercise the concentration is reduced to __
    o   In the decrease from 100 torr in the lungs to 40 torr in resting muscle, the oxygen saturation of hemoglobin is reduced from __ to __, and so __% of the oxygen is released over a drop of __
    §  Because the change in oxygen concentration from rest to exercise corresponds to the steepest part of the oxygen-binding curve, oxygen is effectively delivered to tissues where?
    • 40 torr
    • 20 torr
    • 98% to 77%

    • 21
    • 60 torr

    where it is most needed
  7. ·         Oxygen binding markedly changes the quaternary structure of hemoglobin

     The cooperative binding of oxygen by hemoglobin requires that the binding of oxygen at one site in the hemoglobin tetramer do what? Because of the __, __ are not possible. Thus, indirect methods for __ must be at work. These mechanisms are intimately related to the __
    • binding of oxygen
    • influence the oxygen-binding properties at other sites
    • large separation between the iron sites
    • direct interactions
    • coupling the sites
    • quaternary structure of hemoglobin
  8. ·         Oxygen binding markedly changes the quaternary structure of hemoglobin

    o   Hemoglobin changes greatly when oxygen binding: the __ and __ are most affected by this structural transition—how? 

    3) o   The quaternary structure observed in the deoxy form of hemoglobin, __, is often referred to as the __ because __
    a1b1 and a2B2 dimers

    they are freer to move with respect to one another in the oxygenated state than they are in the deoxygenated state


    • T (for tense) state
    • it is quite constrained by subunit-subunit interaction
  9. ·         Oxygen binding markedly changes the quaternary structure of hemoglobin

    4) o   The quaternary structure of the fully oxygenated form, __, is called the __. In light of the observation that the __ of hemoglobin is __, the __ and __ designations seem appropriate. 
    • oxyhemoglobin
    • R state
    • R form
    • less constrained
    • tense and relaxed
  10. Importantly, in the R state, the __ are free of __ and are capable of __. By triggering the shift of the hemoglobin tetramer from the T state to the R state, the binding of oxygen to one site does what?
    • oxygen-binding sites
    • strain
    • binding oxygen with higher affinity than are the sites in the T state

    increases the binding affinity of other sites
  11. ·         Models to explain hemoglobin cooperative binding of ligands to a multisubunit assembly like hemoglobin are two: 

    Explain the first
    concerted model (MWC): the overall assembly can exist in two forms: the T and R states

    The binding of ligands shifts the equilibrium between the two states.

    As a hemoglobin tetramer binds each oxygen molecule, the probability that the tetramer is in the R state increases. Deoxyhemoglobin tetramers are almost exclusively in the T state, but binding oxygen to one site shifts equilibrium to the R state

    If a molecule assumes the R quaternary structure, oxygen afinity increases and oxygen binds more. 

    Thus, the binding curve is shallow at low oxygen concentrations when all of the molecules are in the T state, become steeper as the fraction of molecules in the R state increases, and flattens out again when all of the sites within the R state molecule become filled. 

    Each tetramer only exists in either R or T.
  12. ·         Models to explain hemoglobin cooperative binding of ligands to a multisubunit assembly like hemoglobin are two: 

    Explain the second.
    o   Sequential model: binding of a ligand to one site increases binding affinity of neighboring sites without fully converting T to R state
  13. ·         Models to explain hemoglobin cooperative binding of ligands to a multisubunit assembly like hemoglobin are two: 

    Explain the second.
  14. Which model is correct.
    ·         Neither model in its pure form fully accounts for hemoglobin’s behaviorà combined model
  15. o   Hemoglobin behavior is concerted in that the __is almost always in the quaternary structure associated with the __state. The remaining open binding site has an affinity for oxygen more than __ greater than that of __. However, the behavior isn’t fully concerted because __

    §  Yet, this molecule binds oxygen three times as strongly as does fully __, an observation consistent only with a sequential model
    • tetramer with three sites occupied by oxygen 
    • 20-fold
    • fully deoxygenated hemoglobin binding its first oxygen
    • hemoglobin with oxygen bound to only one of the four sites remains primarily in the T-state quaternary structure

    deoxygenated hemoglobin
  16. ·         Oxygen binding causes each iron atom in hemoglobin to move how--> what then happens?--> what is the effect? --> __
    o   The structural transition at the iron atom in one subunit is __--> pathway of __ for __
    from outside the plane of the porphyrin into the plane

    histidine residue, which is part of the alpha helix, bound in the fifth coordination site moves with it, causing the helix to move

    the carboxyl terminal end of this alpha helix lies in the interface between the two alpha-beta dimers

    directly transmitted to the other subunits

    communication for cooperative binding

    T to R transition
  17. ·         For hemoglobin to function efficiently, the T state must __until the __ has done what? . The T state of hemoglobin is highly __, pushing the equilibrium so far toward the R state that __--> another mechanism is needed
    remain stable 

    binding of sufficient oxygen

    has converted it into the R state


    little oxygen would be released in physiological conditions
  18. o   Discovered by comparing oxygen-binding properties of hemoglobin in RBCs with fully purified hemoglobin
    §  Pure hemoglobin binds oxygen much more tightly than does hemoglobin in RBCs due to __, which without it, what would be happen? 
    2,3-bisphosphoglycerate, without which hemoglobin would be unable to transport oxygen efficiently
  19. §  Why does 2,3-BPG do this? 
    • · A single molecule of the 2, 3- BPG binds in the center of the tetramer, in a pocket present only in the T form. When T switches to R, this pocket collapses and 2,3-BPG is released (bonds must be broken)
    • o   In the presence of 2,3-BPG, more oxygen-binding sites within hemoglobin tetramer must be occupied in order to induce the T-to-R transition, and so hemoglobin remains in the lower-affinity T state until higher oxygen concentrations are reached
    • · 2,3-BPG is an allosteric affector, binding to a site that is completely distinct from that for oxygen
  20. Binding 2,3- BPG also has other consequences
    o   Human fetal hemoglobin tetramers have two __ and __, the gamma of which is __ identical in amino acid sequence with the B chain. Substituting serine for His in the B chain, part of the 2,3-BPG-binding site, causes what? 
    • alpha and two gamma chains
    • 72%
    • removal of two positive charges and reduces the affinity of 2,3-BPG.
  21. §  Consequently, the __of fetal hemoglobin is __than that of maternal (adult) hemoglobin, which allows __
    • oxygen-binding affinity 
    • higher
    • oxygen to be effectively transferred from maternal to fetal red blood cells
  22. ·         Carbon monoxide is a colorless, odorless gas that binds to hemoglobin at the same step as oxygen, forming carboxyhemoglobin, which devastates normal oxygen transport: 

    What's the first reason? 
    o   First, carbon monoxide binds to hemoglobin about 200-fold more tightly than does oxygen, preventing its delivery
  23. ·         Carbon monoxide is a colorless, odorless gas that binds to hemoglobin at the same step as oxygen, forming carboxyhemoglobin, which devastates normal oxygen transport: 

    What's the second reason? 
    o   Second, carbon monoxide bound to one site will shift the oxygen saturation curve of the remaining sites to the left, forcing the tetramer into the R stateà increased affinity for oxygen, preventing its dissociation at tissues
  24. What is the treatment for CO poisoning?
    o   Treatment of carbon monoxide poisoning is administration of 100% oxygen at high pressure to allow it to displace carbon monoxide