Lecture #4 and #5 - Haemoglobin as a model protein Flashcards
Myoglobin (monomer):
- How many alpha and beta parts?
- Where is the iron atom?
- Where is the heme group?
- How is the heme held in place?
- What is a heme?
- Why is myoglobin known as globin-type protein?
- ____ protein subnit
- Is the high-affinity oxygen binding reversible?
- Where is it mostly found?
- An iron-containing cyclic compound found in cytochromes, haemoglobins and myoglobin
Heme group:
- How rings and how many and linked by what?
- Heme is an isomer of what? Describe the isomer (4) and what heme evolved to do (1)
- What state is Fe in and why?
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Myoglobin:
- Can CO2 interact with myoglobin and haemoglobin and if so, where does it interact?
- Heme is a planar tetrapyrole ring system with iron in the middle. How many co-ordinations does Fe have and where do they bind?
- What two histidines are involved with the heme and what do they each do?
- What competes for O2 and what can you say about its binding affinity?
- Cyanide - what does it bind to and its main inhibitory effect is at what?
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If you got CO poisoning, what do you do?
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Haemoglobin (a tetramer - 4 globin proteins)
- How many O2 can it bind so it must have how many subtypes - describe their similarity (are they alpha helices and beta sheets or what?)
- Is it all alpha helixes?
- Is it a transporter of blood oxygen or a store?
- Does it have higher affinity with O2 compared to myoglobin?
- What type kinetics for multi-subunit proteins like haemoglobin?
- Briefly describe the binding/release of O2 in haemoglobin
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Co-operative oxygen binding to haemoglobin
- Why doesn’t it happen with myoglobin?
In the case of haemoglobin, the binding of oxygen to one subunit of the haemoglobin tetramer, induces what?
This conformation change is transmitted to adjacent subunits which makes the binding of oxygen to those subunits _____
The binding of oxygen to haemoglobin is _______
In the case of haemoglobin, the binding of oxygen to one subunit of the haemoglobin tetramer, INDUCES A CONFORMATION CHANGE IN THE SUBUNIT
This conformation change is transmitted to adjacent subunits which makes the binding of oxygen to those subunits EASIER
The binding of oxygen to haemoglobin is CO-OPERATIVE`
R and T states - explain them
Generally, oxyHb is the R state Hb and deoxyHb is the T state Hb, but there can of course be O2 bound in either of the states. If three O2 are bound some casually say oxyHb while technically it’s more correct to say partially oxygenated Hb. Theoretically if there are 3 O2 bound, it’s pretty likely Hb will be in the R state (oxyHb), but it can be in the T state (deoxyHb). Similary, if only one O2 is bound, the more correct term would be partially deoxyganated Hb. If two O2 are bound, partially oxygenated or partially deoxygenated works one really should consider the configuration Hb is in.
BPG binds much much easier to the deoxy state becasue of the pocket formed when Hb is in the T state configuration. IF it manages to bind (very unlikely though) to the R state, any oxygen attached will be released. However, remember that when the fully oxygenated Hb (R state configuration) is on its way from the lungs to muscle, when it gets close to the tissue, where there is low oxygen pressure, it will start dropping the O2 off. When e.g. two of the four O2 has left the R-state Hb (which is now partially deoxygenated), the Hb may switch to the T-state configuration. When in the T state configuration, the remaining two O2 will be released much easier becasue this configuration has a much lower affinity to O2. Equally important is that when in the T-state at the tissue, it prevents any released O2 from rebinding. So, as O2 is being released at the tissue, at some stage the Hb will switch over to the T state (the fewer O2 are bound the more likely the R to T state switch is). This is importand becasue you don’t want the O2 that has just been released to have high affinity for the Hb and bind back to it. You want the O2 to be available for the tissue, which it won’t be if it has a high affinity for the Hb and binds back to it.
Also look at tutorial and the booklet
What happens when O2 binds?
When oxygen binds to deoxyhaemoglobin the Fe2+ moves into the plane of the porphyrin ring and draws the His F8 down, leading to repositioning of the F helix
2,3-BPG binds where in and in what kinda haemoglobin?
Where is more BPG found?
What does it do?
How does it bind to the middle? Like describe the things involved.
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In the presence of BPG, what happens to oxygen affinity?
What happens to the curve?
So this effect contributes to what?
In lungs, what does the high pO2 do?
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Bohr effect
- What does it relate to?
- The equation - explain it all
HbO2 + H+ + CO2 —(actively metabolising tissue e.g. muslce—-> O2 + Hb-CO2-H+
- What can CO2 be buffered by?
- Decrease in pH leads to what happening to the affinity?
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As you increase the three things, what happens to the curve and what do you reduce?
In actively metabolising tissue, is the pH high or low?
Left and right shift - what happens to the affinity?
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Go have a look at the buffer system thing - 2nd to last slide
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Summary
Myoglobin is a ______ displaying high affinity binding of oxygen which suits its role as a tissue oxygen ______ system
Haemoglobin is a ______ with a role in blood oxygen transport between lungs and peripheral tissues.
High pO2 (lungs) results in ______ of BPG from deoxy- haemoglobin (and there is release of H+ and CO2) followed by oxygen binding to haemoglobin which is transported in the blood to peripheral tissues.
In the vicinity of aerobic metabolising peripheral tissues H+ and CO2 are elevated and pO2 is relatively low - these factors promote the ______ of oxygen from haemoglobin - which is facilitated by binding of ______ to deoxy-haemoglobin
Myoglobin is a MONOMER displaying high affinity binding of oxygen which suits its role as a tissue OXYGEN storage system
Haemoglobin is a TETRAMER with a role in blood oxygen transport between lungs and peripheral tissues.
High pO2 (lungs) results in DISPLACEMENT of BPG from deoxy- haemoglobin (and there is release of H+ and CO2) followed by oxygen binding to haemoglobin which is transported in the blood to peripheral tissues.
In the vicinity of aerobic metabolising peripheral tissues H+ and CO2 are elevated and pO2 is relatively low - these factors promote the RELEASE of oxygen from haemoglobin - which is facilitated by binding of BPG to deoxy-haemoglobin
