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9 Cards in this Set
- Front
- Back
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Discuss how the R(elaxed) and T(ense) configurations relate to the positioning of the heme iron, the role of the proximal histidine, and the binding or releasing of oxygen
Tense configuration |
Tense configuration (T; deoxy) of Hb has lower oxygen affinity and salt bridges among its residues that confer stability on the protein. The iron is pulled away from the plane of the heme (makes it more difficult for oxygen to bind). More likely to release oxygen. The proximal histidine is bound to iron; as long as oxygen is not bound, the histidine is not pulled and will not rotate the protein to expose another binding site for oxygen.
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Discuss how the R(elaxed) and T(ense) configurations relate to the positioning of the heme iron, the role of the proximal histidine, and the binding or releasing of oxygen
Relaxed configuration |
Relaxed configuration (R; oxy) has higher oxygen affinity and the salt bridges between its residues are lost due to rotation. The binding of oxygen pulls the iron into the plane of the heme and helps to stabilize the R state (not very stable on its own, but has higher affinity for oxygen with or without an oxygen already bound). More likely to bind oxygen. Pulling of iron into the plane of heme also pulls the proximal histidine, which is bound to iron. The twists the configuration of the protein, exposing another active site for oxygen to bind. (Cooperative binding)
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Describe how cooperative binding of oxygen by hemoglobin improves its effectiveness as an oxygen transporter
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When oxygen binds to iron, it induces a change to the R form in those other subunits by pulling iron into the plane of heme and also pulling the proximal histidine (conformational change of the protein). This ruptures salt links in other parts of the protein, freeing up another subunit to bind to oxygen. This characteristic gives Hb a sigmoid affinity curve for oxygen. In the lungs where PO2 is high, Hb is saturated. In the tissues where PO2 is lower, Hb affinity for oxygen is lower and the oxygen can be released from Hb to be delivered to the tissues.
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Discuss the physiological significance of protons (Bohr Effect) on the affinity of Hb for oxygen and under what circumstances these effects are important
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○ The Bohr Effect occurs due to metabolism at the body tissues. Protons are a product of metabolism and raise the pH of the tissues. Histidine is basic at physiologic pH and will become protonated (gains a proton and positive charge). Now the histidine+ will interact with other residues, forming a salt bridge and pushing the protein into the T configuration. Oxygen affinity is lower in this configuration and so oxygen is more likely to be delivered to the tissues. During active metabolism, this effect helps to ensure that oxygen dissociates from Hb.
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Discuss the physiological significance of carbon dioxide on the affinity of Hb for oxygen and under what circumstances these effects are important.
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○ Carbon dioxide is also a product of metabolism (aerobic). It enters the cell and binds to Hb at its N-terminus, forming a carbamino group that induces a salt link between the N-terminus and one of the alpha helices. The salt link stabilizes the T form, lowering affinity for oxygen. This also ensures oxygen delivery during active metabolism. Additionally, some carbon dioxide is converted to acid; this allows protonation of histidine in the same fashion as the Bohr effect.
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Discuss the physiological significance of BPG (2,3-bisphosphoglycerate)
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○ BPG (product of RBC when PO2 is low) fits in the cleft that opens when Hb rotates from R to T state. It stabilizes the T state (one per Hb molecule) and decreases oxygen affinity. It allows oxygen to bind cooperatively to Hb.
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Discuss the physiological significance of BPG (2,3-bisphosphoglycerate) and the presence of the γ-subunit rather than the β-subunit in HbF on the affinity of Hb for oxygen and under what circumstances these effects are important.
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- The gamma subunit has fewer positively charged residues that interact with BPG (4 instead of 6 in HbA1), so the binding of BPG is less in fetal Hb. This means that the Hb is more likely to be in the R form; fetal Hb has a higher affinity for oxygen, ensuring that oxygen will move from the mother's Hb to the fetus.
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Discuss how carbon monoxide (CO) competes with oxygen for binding to Hb and how its greater affinity relative to O2 is reduced by the distal histidine.
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Carbon monoxide also binds to the ferrous iron in Hb, with a 200x greater affinity than oxygen. It is sterically hindered by the distal histidine from binding straight on (if it were able to do this, affinity would be 10,000x
higher). CO is highly toxic. |
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Describe the relationship between hemoglobin and acid-base homeostasis.
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The body has a buffer system (with weak acids) to prevent changes in pH. Hb absorbs 50% of aerobically produced protons on the histidine residues 15% of metabolic CO2 binds to the N-termini of globin chains, so it cannot react with water to form H+. Hb helps prevent metabolic acidosis
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