Ch 7.1 Lecture

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Ch 7.1 Lecture
2014-10-11 23:37:41
Test Two
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  1. Compare myoglobin and hemoglobin.
    • proteins need prosthetic groups because amino acids don't bind iron and oxygen--> heme, specificalyl protoporphyrin IX
    • -- 4 pyrrole rings--> side chains attached

    • 6 coordination (binding) sites
    • --> iron is held tightly and can bind to numerous substituents

    inorganic Fe2+ or Fe3+ oxidation state
  2. Explain sperm whale myoglobin.
    153 amino acids

    75% alpha helix folded into a compact structure 

    8 helices


    proline terminates four of the helices; when you see proline, it's the end because a kink isn't conducive of an alpha helix
  3. What is a good animal source of myoglobin and why?
    whale because they store oxygen for long periods

    Plenty of myoglobin tissue

    One whale can enable a lot of myoglobin to be isolated

    -->stable form of myoglobin--> easy to crystallize
  4. Explain the structure of myoglobin.
    hydrophobic inside; hydrophilic outside

    -> 2 histidine residues located inside: important. It is polar, yet it is located inside. 

    • The heme fits into the crevice n the surface
    • --> polar faces of heme--> outside

    nonpolar surfaces by nonpolar portions of protein 

    Heme needs to be bound by some way. It is bound by histidines.
  5. What are the two hemes called in myoglobin and what do they do?
    proximal involved in covalent bonds with coordinate position 5 of iron

    Distal: opposite side; not bound but it takes up an important space on the other side
  6. What does the proximal histidine do?
    pulls iron out of plane 

    When oxygen binds to iron at position six, iron gets pulled up inot the heme, and it flattens out. 

    Oxygen is bound at an angle
  7. What does the distal histidine do?
    it comes in at an angle, giving oxygen fighting ability against CO

    It prevents oxygen from coming in straight. 

    CO competes with oxygen for binding/ it is 25k times more efficient in binding if it is allowed to bind straight
  8. Comparison of tertiary structure of myoglobin and hemoglobin
    very related structurally, but not primary sequence wise. Not many of the amino acids are similar
  9. Explain hemoglobin briefly
    it is a tetramer: four subunits--2 alpha chains and 2 beta chains

    four subunits come into contact and interact with each other. THey have to fit into each other well--> held together
  10. In the entire sequence of human hemoglobin and sperm whale myoglobin, what is unique?
    there are only two similar amino acids that have been conserved in the entire protien
  11. What is histidine used for in hemoglobin?
    need it to hold genes and block binding of other molecules
  12. What is the function of glycine in hemoglobin?
    allows the close approach of the B and E helices. Tiny amino acids so the helices can approach each other properly
  13. Explain the oxygen saturation curve for myoglobin.
    a graph of how much saturation is occurring versus how much O2 is available in the environment leads to a curve that rises very rapidly and levels off rapidly
  14. Explain the oxygen saturation curve for hemoglobin.
    sigmoidal shaped. 

    • When there is less oxygen, it is harder time to bind to oxygen. It doesn't want to
    • When tere is alot of oxygen, it is easier to hold on
  15. Why is there such a difference in the curves?
    • four subunits of hemoglobin act cooperatively.
    • Subunits shift between T and R conformation

    • Relaxed holds on better
    • TEnse lets go easily
  16. In terms of release, how much does hemoglobin drop off?
    two thirds; with cooperativity, you can get saturated
  17. How much does myoglobin release?
    seven percent
  18. Without cooperativity, how would hemoglobin behave?
    It would be a really long time to get saturated, which is bad, and results in a release of only about 38%
  19. What are the changes that take place when bound to oxygen?
    space in the middle of the hemoglobin is barelly seen in oxyhemoglobin

    the hemes are not in the same place

    roation of the subunits around an imaginary axis is about 15 degrees
  20. All changes are related to __. explain.

    iron gets pulled up into heme when oxygen binds. histidine gets pulled-> helix is pulled--> interface is affected
  21. Explain the concerted model?
    all four cubunits change in concert. 

    When no oxygen is bound, the T state is strongly favored--> As we bind, it is still tense, but the more oxygen leads to a greater chance that it will shift from T-->R

    It is not likely to change if only one oxygen is bound

    Binding of O2 pushes the entire tetramer toward relaxing--> more likely to stay relaxed
  22. Explain the sequential model.
    we start with 4 Tense units; one oxygen causes relaxation in one, influencing adjacent subunits to relax. You don't have to change all at once. 

    One at a time

    as one relaxes, it influences the others to dod so as well
  23. What is the model?
    Based on the oxygen saturation curve, it is clear that it is a mixture of both. At the very beginning of the curve, it resembles the sequential model. However, as you get to the top, it resembles the concerted model
  24. Structurally, what does deoxyhemoglobin do?
    it pulls on the iron

    Binds into 6 coordination position--> iron gets pulled into heme, flattening out. Histidine gets pulled with it and the entire polypeptide chain gets tugged--> tug is felt at the surface
  25. The T form is stabilized by what?
    weak interactions between specific amino acids
  26. Once oxygenation occurs, what happens?
    changes around the heme are translated onto the surface where they shift. 

    The cavity disappears. And, 2,3-BPG goes in the caivty
  27. Explain 2,3-BPG
    In the deoxy state, conformation of all the subunits is tense. The cavity is open. 2,3-BPG goes right into the cavity to keep it open.

    2,3- BPG interacts with amino acid side chains and is held in place
  28. What happens if BPG is not there?
    the curve looks like myoglobin's curve. 

    BPG is critical in deliverance of O2 to the tiessues. In absence, o2 stays bound to hemoglobin
  29. BPG interacts through?
    H bonds, electrostatic interactions, etc.
  30. Oxygen can jump form the __ to the __ because it goes to the __.
    • mother to fetus
    • relaxed hemoglobin of the fetus
  31. Why is the fetal saturation curve slightly higehr than maternal?
    changes can occur that allow mom to transport O2 to fetus

    O2 flows from maternal oxyhemoglobin to fetal deoxyhemoglobin. Changes can occur that allow this transport.
  32. Why does this transfer to fetal hemoglobin occur?
    it can occur because fetal hemoglobin has higher affinity for O2 and lower affinity for 2,3-BPG

    2 histindes are replaced with serines, lowering the affinity for 2,3-BPG for binding site, meaning hemoglobin spends more time relaxed. 

    Fetal red blood cells hold onto oxygen much longer. As O2 is flowing, very little transfers to fetal if the hemoglobin is the same
  33. What happens during a workout?
    • you forget to breathe--> not enough O2--> anaerobic--? lactic acid buildup
    • --> pH of tissue changes
    • --> extra proteins interact with hemoglobin and help lower molecules affinity for O2

    • Protons taken up by two histidine residues that exist in the deprotonated form
    • --> HIstidine is neutral at pH=6. So, that can change. It can acquire positive charges--> ionic bond with other side chains to stabilize the tense conformation of hemoglobin--> allows release of 77% as opposed to 66%
  34. Ionic bonds help maintain __.
    `the tense conformation
  35. In the blood capillary, what else is happening?
    also producing Co2 which reacts with H2O in blood stream--> carbonic acid loses proton to become carbonate
  36. What is the stabililizing effect of excess protons and Co2?
    cause release of O2

    CO2 affects release of O2 by binding to alpha-amino groups in chains--> changes charge and allows amino termini to form ionic bonds--> further stabiliziation of tense form
  37. What is different about the HbS gene?
    on the surface, there is a valine. Hydrophobic is looking for a pocket to hide in. 

    Changes the result in a small hydrophobic pocket. As long as nothing wants to bind, you're okay.

    However, unnatural interactions lead to clumping, precipate can't go trough the capillaries. So, they burst. 

    Valine finds a pocket and binds into the pocket--> the two subunits are stuck together, then 3 and 4 get stuck--> no longer soluble
  38. How many cells are in your body and how many molecules of hemoglobin does each have?
    • 30 trillion RBCs
    • each has 280 million hemoglobin
  39. What does hemoglobin do? Where doe sit go?
    oxygen carrier; carries carbon dioxide as well

    capillaries fit RBCs one at a time
  40. Hemoglobin and Myoglobin structure
    H: unique in that it is allosteric; bound oxygen is one shape; unbound is the other shape

    Myoglobin: storing proteins; doesb't leave cells in muscle tissue; structurally related to hemoglobin
  41. Sickle cell anemia
    regular red blood cells have a size that is conducive to the movement through the capillary

    sickle cells get stuck and jam up-- pressure causes them to burst

    last about twenty days--> not enough cells--> not enough hemoglobin
  42. Crystals:
    hemoglobin precipitates in sickle cell (no longer soluble)-> shape change--? problems
  43. Linus Pauling
    took normal hemoglobin and sickle cell hemoglobin and ran a modified gel. The different bands and reacting and migrating differed in chanrges--> something led to charge difference on gel
  44. 1950s?
    they separated by size and pI

    • Beta subunit causes the problem. Scientists purified and lit it up
    • Separated by MW and pI

    One fragment has the tissue.

    They sequenced it and saw a point mutation

    • Glutamic acid--> valine
    • negative--> hydrophobic