Term
| Why do hemoglobin and myoglobin exist |
|
Definition
| Because O2 has limited solubility in blood |
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Term
| Primary function of myoglobin |
|
Definition
| store oxygen in muscle for release during periods of oxygen deprivation |
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Term
| Quaternary structure of myoglobin |
|
Definition
| None. Monomeric protin with heme grop |
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Term
| Primary function of hemoglobin |
|
Definition
| carry oxygen from lungs to tissue |
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Term
| Quaternary structure of hemoglobin |
|
Definition
| Composed of 2 alpha and 2 beta subunits with heme group |
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Term
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Definition
| 8 helices – 75% helices labeled A,B,C,D,E,F,G, and H. Interior consists predominantly of non-polar residues (Phe, Leu, Val). Acidic and basic residues (Asp, Glu, Lys, Arg) are on the surface. All peptide bonds planar and trans |
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Term
| Location of heme group in myoglobin |
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Definition
| In crevice, surrounded by nonpolar residues except proximal His F8 and E7 |
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Term
| Why are there nonpolar residues near heme group in myoglobin |
|
Definition
| To protect Fe2+ from oxidation to Fe3+, which will not bind oxygen |
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Term
| Coordination of Fe in heme group |
|
Definition
| 6. 4 nitrogens of pyrrole rings, 1 His93 (F8), 1 either empty, O2, CO, or H2O |
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|
Term
| What is so important about distal histidine (E7) |
|
Definition
| reduces space, forcing O2 to bind at an angle, which is what it prefers |
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Term
| Ox state of Fe and 5th and 6th coordinates of deoxymyoglobin |
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Definition
| Fe 2+, 5th and 6th coordinates are His F8 and empty |
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Term
| Ox state of Fe and 5th and 6th coordinates of oxymyoglobin |
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Definition
|
|
Term
| Ox state of Fe and 5th and 6th coordinates of ferrimyoglobin |
|
Definition
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|
Term
| Binding of CO to heme group in myoglobin |
|
Definition
| Bent due to distal His 64 (E7). Strongest binding would be straight |
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Term
| Change in CO affinity for heme compared to O2 in Hb and Mb |
|
Definition
| Heme alone binds CO 23000x better than O2, but only 200x better in Mb and Hb |
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Term
| Differences in O2 binding in Mb and Hb |
|
Definition
| In Mb, O2 binding is non-cooperative, O2 affinity is independent of pH, CO2 and 2,3BPG. in Hb, O2 binding is cooperative. O2 affinity is dependent on pH, CO2 and 2,3BPG |
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Term
|
Definition
| events at one active site of one subunit can influence events at active sites of other subunits |
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Term
| MWC Model of Cooperativity |
|
Definition
| Concerted model; allosteric changes occur in unison |
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|
Term
| KNF Model of Cooperativity |
|
Definition
| Sequential model, Allosteric changes occur sequentially |
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Term
| How to think of Hb Cooperativity |
|
Definition
| As a series of equilibria. Without O2, T state is strongly preferred. As O2 binds, the R state becomes more and more preferred |
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|
Term
| Relation observed hemoglobin oxygen-binding curve and those of R and T state |
|
Definition
| Observed is between the R and T states, more similar in shape to R than T state curve. |
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|
Term
| What are the major players in cooperative oxygen binding in hemoglobin |
|
Definition
| O2, H+, CO2, 2,3BPG (also known as DPG or 2,3-bisphosphoglycerate) |
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|
Term
|
Definition
| DeoxyHb exists in T (tense) state. It has reduced affinity for oxygen |
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|
Term
|
Definition
| OxyHb exists in R (relaxed) state. It has higher affinity for O2. |
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Term
| Effect of CO, H+ and BPG on state of Hb |
|
Definition
| all increase the proportion of T state subunits |
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|
Term
| Key residues of Hb (just names not role) |
|
Definition
| Gly25, His E7 (H63), His F8 (H92), Asp94, Val98, His146, Tyr145 |
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|
Term
|
Definition
| needed for close association of B and E helices |
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|
Term
|
Definition
| salt link with imidazole His146 (protonated) |
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|
Term
|
Definition
| hydroxyl group forms H-bond with Val98 carbonyl in hydrophobic cavity |
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|
Term
|
Definition
| carboxyl group forms a salt link with Lys40 from alpha-chain. When this carboxyl salt link breaks, it tells the alpha chain that the beta chain has a bound oxygen |
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Term
| In Hb, how does the alpha chain know that the beta chain has a bound oxygen? |
|
Definition
| beta chain has a bound oxygen if the salt link breaks between carboxyl group of His146 and Lys40 from alpha-chain |
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|
Term
| Features of globin pocket of Hb |
|
Definition
| Hydrophobic pocket protects Fe of heem group from oxidation. Lys side-chains i/a with propionic side-chains to position heme in pocket. Hydrophobic surface of Hb necessary for subunit-subunit i/as. |
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|
Term
| What is the conformational change in Hb after O2 binding |
|
Definition
| Oxygenation causes one alpha-beta dimer to rotate around a pivot point 15 degrees relative to the other alpha-beta dimer |
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Term
| Differences in oxygen-binding curves of Mb and Hb |
|
Definition
| Mb curve is hyperbolic. Hb curve is sigmoidal. For all partial pressures of O2, myoglobin binds oxygen more tightly than Hb |
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Term
| Does Hb or Mb unload more oxygen in response to a small decrease in oxygen partial pressure |
|
Definition
| Hb due to sigmoidal shape |
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Term
| Does HbF or HbA bind O2 more tightly? |
|
Definition
| HbF binds O2 more tightly for all [O2] |
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|
Term
| How does 2,3BPG affect O2 binding of Hb |
|
Definition
| Its negative charges bind to deoxyHb via electrostatic i/a's with basic aa residues in Hb. |
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|
Term
| What is the aa substitution in HbF |
|
Definition
|
|
Term
| Does BPG bind to Hb better in T form or R form/ |
|
Definition
|
|
Term
| Affinity for BPG in HbF vs HbA |
|
Definition
| HbF has lower BPG affinity, which shifts equilibrium to R form |
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