Myoglobin & Hemoglobin Flashcards
In which human organ is myoglobin (Mb) most important?
Heart - where rapid oxygen supply is needed.
Explain the causes and importance of a right shift in the Hb/O2 binding curve.
Right shift in the Hb/02 binding curve is often caused by decreased pH (increase in H+), increased C02, increased 2,3-BPG or an increase in temperature. All of these lead to increased 02 unloading which means a higher O2 deliver to tissue
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 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 sites to become available
What is the Bohr effect?
It involves a right shift when pH decreases. Oxygen release from Hb is enhanced when the pH is lowered, or when the C02 is high, so Hb has a decreased 02 affinity. When raising the pH or lowering the C02 it causes a left shift and greater O2 affinity.
What is the physiological importance of cooperativity in Hb function?
Hb has 4 subunits where the binding of an 02 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, H+ and C02. 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 affect. Hb cannot readily bind the first 02. But once the first 02 binds, subsequent 02 molecules bind with higher affinity. Because of Hb’s sigmoidal 02 dissociation curve, Hb can respond more readily to small changes in partial pressures of oxygen. Mb has a hyperbolic 02 dissociation cuve. This means it will reach 02 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?
- They weaken the avidity of the heme-O2 interaction. Heme binds 02 so strongly that it can convert 02 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 binds to a binding site between to beta chains, where they 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?
Adult Hb have beta chains that interact with 2,3-BPG. Fetal Hb have 2 gamma chains instead of beta chains and without the beta chain, fetal Hb are not affected by 2,3-BPG levels. Fetal Hb can have a greater affinity for 02 and often will take 02 from maternal Hb.
What does the Hill equation describe?
Cooperativity n = cooperativity n = 1 (no cooperativity) n < 1 (negative cooperativity) n > 1 (positive cooperativity)
How does NO interact with Hb, and what is the physiological significance of that interaction?
Under low oxygen conditions, Hb can convert NO2- into NO. Hemoglobin can reversibly bind to NO, both at the heme iron and at the cysteine residues in the globin chains. NO acts as a relaxant for vascular smooth muscle. Hb can pick up NO and cause increased blood pressure.
