7 - Myoglobin/Hemoglobin Flashcards
In which human organ is myoglobin (Mb) most important?
Myoglobin is most important in the heart where rapid O2 supply is needed.
Explain the causes and importance of a right shift in the Hb/O2 binding curve.
Right shift in the Hb/O2 binding curve is often caused by decreased pH (increased [H+]), increased [CO2], increased [2,3-BPG], or an increase in temperature. All of these lead to increased O2 unloading which means a higher O2 deliver to tissues.
In Hb, how does the binding of the first oxygen molecule affect the binding of the next ones?
Deoxy Hb is generally taut, where the heme groups are restricted, making O2 difficult to bind. Once O2 is bound to the first heme group, the iron of that heme will shift, pulling its attached histidine along. This movement breaks salt bridges, progressively relaxing the Hb molecule to allow more O2 binding site to become available.
What is the Bohr effect?
The Bohr effect involves a right shift when pH decreases (increase of H+ concentrations). Oxygen release from Hb is enhanced when the pH is lowered, or when the [CO2] is high. Hb has a decreased O2 affinity. Raising the pH or lowering the [CO2] will have the opposite affect and shift the curve to the left, resulting in a greater O2 affinity.
What is the physiological importance of cooperativity in Hb function?
Hb has four subunits where the binding of an O2 molecule at one heme group increases the oxygen affinity of the remaining heme groups in the same Hb molecule.
Compare the “behavior” of Mb and Hb with respect to O2, CO2 and H+.
Mb and Hb act very differently with respect to O2, CO2, and H+. Although Mb may have a greater affinity at lower concentrations of O2 than Hb, ultimately Hb can transport more molecules of O2 because of its cooperative effect of multiple binding sites. Also, because of the cooperative effect, Hb cannot readily bind the first O2. But once the first O2 binds, subsequent O2 molecules bind with higher affinity. Because of Hb’s sigmoidal O2 dissociation curve, Hb can respond more readily to small changes in partial pressures of oxygen. Mb has a hyperbolic O2 dissociation curve. This means it will reach O2 saturation much quicker than Hb at a low partial pressure of oxygen. This doesn’t give Mb much flexibility at varied O2 changes, since it stays at max saturation for most of the curve.
How does the protein (globin) portion of Mb or Hb affect the reactivity of heme?
The globins in Hb and Mb have two main functions:
- They weaken the avidity of the heme-O2 interaction. Heme binds O2 so strongly that it can convert O2 to a superoxide anion, an unwanted oxidizing agent.
- It will also prevent the interaction of oxy-heme groups with that of other oxy-heme groups.
How and where does 2,3-BPG interact with Hb? Where does 2,3-BPG come from?
2,3-BPG binds to deoxy Hb, making it more stable and more resistant to oxygenation after O2 delivery. Its negative charge allows it to bind to a binding site between two -chains (where there are several positively charged residues). It will cause a right shift in the O2 dissociation curve. 2,3-BPG is a product of the glycolytic pathway.
How does fetal Hb (HbF) differ from HbA?
Structurally, fetal Hb has two gamma chains instead of beta chains. Thus, 2,3-BPG will not be able to bind to deoxy Hb. Without this feature, fetal Hb can have a greater affinity for O2 and often will take O2 from maternal Hb. Relative to maternal Hb, HbF is left shifted on the O2 dissociation curve.
What does the Hill Equation describe?
The importance of Cooperativity.
How does NO (nitric oxide) interact with Hb, and what is the physiological significance of that interaction?
Hb can bind NO at the heme iron and cysteine residues in the globin chains. NO acts as a relaxant for vascular smooth muscle (by inhibiting proliferation and migration). Hb can pick up this vasodilator, stiffening vascular tissues, and increasing blood pressure. NO is a very strong vasodilator, so Hb can be used to mediate vascular tone. NO also has antiplatelet effects.
