Term
| Position of Iron and Porphyrin plane in deoxy- and oxyhemoglobin |
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Definition
In deoxyhemogobin, Fe2+ pulled out of the plane due to steric replusion between imidazole of His92 (F8) and the porphyrin ring.
In oxyhemoglobin, iron is pulled back into the porphyrin plane. |
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Term
| Mechanism for oxygen binding in hemoglobin |
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Definition
| In deoxy Hb, Fe2+ is out of the heme plane. O2 binding pulls Fe2+ into the heme plane.Since Fe2+ - His92 form coordinate covalent bond the F helix moves. Movement of helix F initiates a 15 deg rotation of a1b1 with respect to a2b2. Movement of helix F initiates conformational changes telling the a-chain that the b-chain has bound oxygen |
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Term
| Cause of need for conformation change with O2 binding in hemoglobin |
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Definition
| When oxygen pulls iron back into the porphyrin plane, steric strain occurs between Val98 and the pyrrole of the heme group. Shifting the F helix removes this strain. |
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Term
| Key interactions in deoxy form of Hb |
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Definition
| a2-Lys40 amino group with b1-His146 carboxylate. imidazole b1-His146 with b1-Asp94. b1-Tyr145 H-bond with Val98 carbonyl oxygen. |
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Term
| Ease of oxygen binding in T form of Hb |
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Definition
the first oxygen is difficult to bind
Once one molecule has bound, the next 3 bind with increasing ease. Hence the sigmoidal binding curve. |
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Term
| Ease of oxygen binding in T form of Hb |
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Definition
the first oxygen is difficult to bind
Once one molecule has bound, the next 3 bind with increasing ease. Hence the sigmoidal binding curve. |
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Term
| Hb transport of CO2 and H+ |
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Definition
| deoxyHb carries CO2 and H+ from tissues to lungs. Oxygen binding releases CO2 and H+ in the lungs. |
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Term
| affect of CO2 and pH on Hb conformations |
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Definition
| low pH and increased CO2 result in conversion from R to T form, pushing equilibrium from oxy to deoxy form. This causes a release in O2 (T has lower O2 affinity than R)in the tissues. The T form binds H+ and CO2 |
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Term
| Effect on aa i/a's in Hb upon O2 binding |
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Definition
| When oxygen binds, Fe moves into heme plane resulting in movement of the F helix and breaking of the hydrogen bond between Val 98 carbonyl and the Tyr 145 hydroxyl. This results in loss of ionic interactions between the His 146 imidazole and the Asp 94 carboxylate, as well as the His 146 carboxylate and the Lys 40 amino group on the chain. |
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Term
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Definition
| lowering pH (increasing [H+]) or increasing [CO2] causes Hb curve to shift to the right, releasing more O2. |
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Term
| Where does the opposite of the Bohr effect occur? |
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Definition
| In lungs, where high O2 concentration drives Hb to release protons and CO2 |
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Term
| Direct way Hb transports CO2 |
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Definition
Direct Role involves amino terminal Val group. High [CO2] get covalent carbamino adduct R-NH-COO- (formed from terminal amino group)
In “T” form, can make an additional ionic interactions that stabilize carbamino adduct |
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Term
| Indirect way Hb transports CO2 |
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Definition
Indirect Role involves carbonic anhydrase. CO2 has limited solubility and HCO3- has high solubility. Via the
Bohr effect, equilibrium shifts towards formation of Bicarbonate by “soaking up” the H+ to imidazole of His146 |
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Term
| Formation of carbamino-Hb |
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Definition
N-terminal residues of deoxyHb react with CO2 forming carbamino-Hb (N-carboxyl Hb)
CO2 + Hb-NH2 -> H+ + Hb-NH-COO-
Carbamino compounds are the combination of CO2 with terminal amino groups |
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Term
| How much CO2 is transported to the lungs via Carbamino-Hb |
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Definition
Carbamino-Hb accounts for up to 30% of CO2 transport to the lungs. The adduct is stabilized only in T form
In lungs, high pO2 favors R-state and leads to release of the bound CO2 |
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Term
| Hb mutation that causes Sickle Cell (HbS) |
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Definition
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Term
| Cause of sickle cell disease |
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Definition
A specific point substitution in the b-chain (E6V) leads to sickle cell anemia. In this case, Glu6 is replaced with a Val. The Val side-chain creates a hydrophobic patch on the surface of the deoxyHb molecule, causing aggregation via hydrophobic interactions.
The aggregate distorts the shape of the RBC into a sickle.
In deoxygenated form, hydrophobic Val can fit into pocket at the EF corner of b-chain in another Hb molecule
In oxygenated form, the conformational rearrangement makes the EF pocket inaccessible to Val6 |
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Term
| Why does anything that make globin chains more sticky lead to aggregation in the cell |
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Definition
| The concentration of hemoglobin molecules in red cells is very high (340 mg/ml) and the molecules are near the concentration that crystallization occurs. Anything that would make the chains more sticky, would be expected to increase the viscosity of the solution, lower the solubility and cause them to aggregate. |
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