Lecture 7 - Hemoglobin Flashcards
Couple facts about erythrocytes
- They’re produced without a nucleus and there are believed to be about 2^11 of them in the body.
The cell lives for around of 120 days before it’s consumed by lymphocytes. For partially this reason, blood samples provide a good window into the current health of the individual
Describe the Shape of hemoglobin
It’s a tetramer made up of two identical alpha subunits, and two identical beta units, as well as a poryphin ring containing the iron and heme group. The electron cloud of the globin keeps water out, but the iron helps allow oxygen in.
How many alpha-helices are in each globin chain?
What is the reason for this?
8 alpha helices per chain
Alpha helices are more durable than beta sheets, which allows the cell to last it’s lengthy 120 day cycle. And also because beta sheets stick to everything, which is undesirable here.
Describe the difference between the alpha chain and the beta-subunits.
In humans, the alpha subunit is almost always composed of alpha chains (but in other places can be Zeta). The beta subunit is a little more variable. It mostly contains beta chains, but can also include gamma, delta, and epsilon-style chains as well (not totally sure what the structural difference is)
What causes sickle cell anemia
In the unhealthy alpha subunit, the exterior protein has an amino acid transfer between the correct glutamic acid accidentally getting replaced by the hydrophobic valine. This causes the cell to “stick” in a sickle shape and can be severely detrimental genetic disorder
Name
-the 3 types of embryonic hemoglobin
- The single type of fetal hemoglobin
- and the 2 types of adult hemoglobin
(Embryonic):
Hb Gower 1(z2e2), Hb Gower 2(a2e2), and Hb Portland(z2g2)
(Fetal): Hb F(a2g2)
(Adult):
Hb A (a2b2), Hb A2(a2d2)
(About 2% of adults have the functionally similar delta subunit)
Describe the Switch and Lock system of hemoglobin
Hemoglobin has two relative conformations (Tight/Low Affinity, and Relaxed/High Affinity) which modulates whether the oxygen is loaded onto the structure or offloaded.
Furthermore, the switching of one segment of the hemoglobin from tight to relaxed, starts to increase the respective looseness of the rest of the tetramer.
Describe a poryphin ring. How much iron is contained in a standard hemoglobin tetramer.
- Heterocyclic tetrapyrrole
– Planar and hydrophobic
– Bound to globin chain - The iron(s) are bound in the center of the ring (Has to be Fe2+)
- There are four irons bound in hemoglobin (1 per subunit), each of which can bind to one oxygen.
What happens when heme is bound to Fe3+ iron?
The Fe3+ iron isn’t capable of binding to oxygen because it relies on being oxidized by the oxygen to bind to it, which it can’t do in such an already oxidized state.
What negative effect does carbon monoxide have on hemoglobin?
Although Oxygen is designed to bond to the iron in heme, Carbon Monoxide has a 2000% higher affinity. The two histidine structures near the iron help alleviate this somewhat.
Distal histidine doesn’t bind to iron, but it creates a well-defined crevice near the iron, which gives oxygen a better chance of binding. CO- is still faster, but not by as much.
Besides the term Proximal Histidine and Distal Histidine, what other name do these two structures have in hemoglobin?
F8 and E7 respectively. (Not positive why they’re called this. The other names seemed a lot easier to remember)
Hemoglobin’s primarily responsible for transporting oxygen around the body. What are the 4 listed features of hemoglobin that make it ideal for doing this
- Iron binding sight
- Cooperativity
- Reversible Binding
- Allosteric Control (Feedback oriented…sort of)
About What percentage of oxygen is absorbed from the lungs at rest, and during exercise.
Hemoglobin absorbs about 20% of the oxygen out of the lungs during rest. However, during exercise, the body’s needs for more oxygen decrease hemoglobin faster, thereby increasing it’s affinity for more oxygen. During exercise, the affinity increases by about 45% to nearly 65% oxygen absorption.
Myoglobin only has one subunit, which greatly affects it’s affinity for oxygen. Where on the fractional saturation chart does myoglobin fall relative to hemoglobin?
Myoglobin reaches maximum saturation at even low levels of oxygen, so it falls to the left of the hemoglobin line (and has a much steeper slope)
What are the 3 allosteric control effectors for hemoglobin affinity?
H+ (protons, low pH)
CO2
2-3 BPG (Biphosphoglycerate)
Each of these INHIBIT oxygen affinity by binding to a different distinct site (not the active site) and inducing conformational change
Each of these move hemoglobin into the Low Affinity T State
