Biochem EX1 - Hemoglobin Flashcards
In which human organ is myoglobin (Mb) most important? (Hint: Which organ is almost entirely composed of muscle, and pumps blood?)
Heart
Explain the causes and importance of a right shift in the Hb/O2 binding curve.
A right shift is caused by cooperativity of binding sites. It is important because the increased binding allows more oxygen to be bound to the binding sites at higher pO2 of the lungs and more of it to be unloaded at the lower pO2 of the capillary beds.
In Hb, how does the binding of the first oxygen molecule affect the binding of the next ones?
As the first molecule of oxygen binds it causes a conformational change that makes subsequent binding easier.
What is the Bohr effect?
A decrease in the amount of oxygen associated with hemoglobin and other respiratory compounds in response to a lowered blood pH resulting from an increased concentration of carbon dioxide in the blood.
What is the physiological importance of cooperativity in Hb function?
These population of carriers (hemoglobin) are starting out in the lungs saturated carrying all the possible oxygen and as the come out of the lungs and experience lower pO2 they start to release some oxygen. Let’s ask how much oxygen has been unloaded at the vertical dashed line (in the capillaries). The pH 7.4 has unloaded around 0.4 so about 60% is desaturated (delivered that much oxygen) but the shifted curve at the lower pH is much more desaturated (delivered substantially more oxygen). So they are both carrying as much oxygen as they can (same number of binding sites) but with the right shift when you get to a lower pO2 the shifted curve is more unsaturated.
Compare the “behavior” of Mb and Hb with respect to O2, CO2, and H+
Myoglobin has a higher affinity for oxygen at lower concentrations, but Hb has a higher P50. The binding cooperativity for Mb remains constant throughout different oxygen concentrations and Hb has a higher binding ability for each additional oxygen. Mb is not as affected by H+ and CO2 as Hb is. Mb does not have cooperativity.
How does the protein (globin) portion of Mb or Hb affect the reactivity of heme?
The globin portion encloses the heme molecule and does not allow oxygen to attack it from a 180 degree angle which would cause iron to give up an electron to oxygen, forming ferric heme and a superoxide.
Does the refrigerator light really go out when you close the door?
Yes
How and where does 2,3-BPG interact with Hb? Where does 2,3-BPG come from?
2,3-BPG is an enzyme in red blood cells. 2,3-BPG binds to the deoxy form of hemoglobin at a space between the two beta chains that is lined with positive charges formed by the ends of the beta chains. The little pockets match the charges on the 2,3-BPG and that causes a right shift is to say that the 2,3-BPG increase favors the deoxy form of hemoglobin
How does fetal Hb (HbF) differ from HbA?
The fetus has a constituency of its hemoglobin of alpha 2 gamma 2 while adults have apha2 beta2. The fetus does not have beta chains, the adult does not have gamma chains.
What does the Hill Equation describe?
The Hill Equation describes the cooperativity of oxygen binding sites in hemoglobin or myoglobin. The Hill equation allows us to calculate the quality of the carrying capacity of an oxygen binder.
The Hill coefficient:
n = 1 (no cooperativity)
n < 1 (negative cooperativity)
n > 1 (positive cooperativity) for hemoglobin it is 2.8
How does NO (nitric oxide) interact with Hb, and what is the physiological significance of that interaction? Consider the many parts of this question.
Hemoglobin has also been noted to catalyze the generation of the vasodialator nitric oxide from nitrite in the blood. It happens under low oxygen concentrations (deoxy hemoglobin) and what happens is that mostly you have deoxy hemoglobin at low oxygen concentrations but when nitrite combines with the hemoglobin iron it depends on a redox reaction that leaves the hemoglobin oxidized, even though you get a molecule of the powerful vasodialator Nitric Oxide.
