Oxygen binding geometry in hemoglobin

N

Nasor

Valued Senior Member
Does anyone here understand why oxygen binds to the iron in hemoglobin in a 'bent' manner? Looking at the orbitals, I would expect it to bind linearly.
 
Isnt it the shape of the surrounding groups that counts as well? I did this 5 years ago in my chemistry degree so have copletely forgotten, but I might find something later on today.
 
Even though I have no idea how Oxygen binds to iron I will give you my idea why. My best guess is that a hydrogen bond forms between the oxygen and iron which naturally causes the molecules to bend. A good example is the hydrogen bond between the base pairs in DNA causing it to bend creating the double helix.

Or I could be completely wrong :D, I'm just learning now.
 
Well, Votorx, your idea is good, but there's a problem. Hydrogen is, by definition, required for a hydrogen bond. However, you're correct in assuming that the electron clouds are distorted when the atoms come together.

Nasor, I have no idea about this, unfortunately. I can try and find something for you though.
 
To quote my textbook"the chemistry of the elements" by greenwood and Earnshaw:
In Haemoglobin which has no O2 attached, (and is therefore known as deoxyhaemoglobin), the iron is present as high spin FE2 and the reversible attachement of O2 )giving oxyhaemoglobin) changes thsi to diamagnetic, low spin Fe2 without affecting the metals oxidation state. ......... The key to the explanation lies in (a) the observation that in general the ionic radius of Fe2 (and also for that matter of Fe3) decreases by roughly 20% when the configuration changes from high to low spin, and (b) the structure of haemoglobin."

Essentially, the Fe is coordinated with 5 nitrogens, one of which is a large imidazole nitrogen group, which means its configuration is as a squat pyramid, the bottom being made up by the 4 nitrogens of the porphyrin ring, which ring is too small for the coordinated Fe2 to fit inside. ACtually, trying to digest several paragraphs of coordination biochemistry down to a post is very hard, especially since I'm just coming off night shift. Would you mind refining your question so that I can address it more closely, or say if this has helped your comprehension of the structure of haemoglobin?
 
When you look at the square pyramidal geometry of the iron-porphyrin/oxygen complex, it would seem to me that the most favorable bonding arrangement would be with the oxygen atoms in the O2 molecule linear to the iron. That would allow the oxygen's sp hybrid orbital to have a strong sigma interaction with the iron's dz^2 orbital, and the oxygen's px and pz orbitals would have pi interactions with the dxz and dyz iron orbitals.

Instread it apparantly prefers to bond in a 'bent' fassion.
 
I think the idea is to make it as reversible as possible, and the stronger the interaction of the iron and oxygen, the harder that is.
I've certainly forgotten a lot of chemistry.
 
guthrie said:
I think the idea is to make it as reversible as possible, and the stronger the interaction of the iron and oxygen, the harder that is.
Click to expand...
This is true - however, although the bent binding geometry is beneficial, I still don't understand why it happens.
 
Hemoglobin, unlike hemecyranin or other biological oxygen transporters has positive oxygen binding cooperation: When one oxygen molecule binds to one of Hemoglobin's 4 heme groups the Hemoglobin alpha-beta protein groups twist in relation to each other, opening up the other 3 heme groups and increasing their affinity for oxygen. So when 1 oxygen bonds, 3 more bond very quickly. This makes hemoglobin much more effective at grabbing oxygen at high pressures and releasing oxygen at low pressures.
 
This makes hemoglobin much more effective at grabbing oxygen at high pressures and releasing oxygen at low pressures.
Click to expand...

First of all, all that was said in the link given in the second post above.

Second, it actually seems to indicate that it is not about pressure but rather about the chemical makeup of the area.

As oxygen binds to the deoxyhemoglobin, a hydrogen ion is released. The hydrogen ion in turn causes the release of carbon dioxide from the blood into the lungs.

As the first oxygen is bond to one of the four heme groups, the protein begins to undergo small shifts in the structure, but sufficient to expel BPG (2,3-bisphosphoglycerate ion). This molecule resides in the "cleft" between the protein chains.
Click to expand...

And.

When the oxyhemoglobin reaches the vicinity of the tissue cells, carbon dioxide, in excess from metabolism which has used up the oxygen supplies, causes an increase in hydrogen ions. The increase in hydrogen ions then initiates the process for the hemoglobin to release the oxygen to the cells. Again BPG begins to work its way into the hemoglobin and causes faster loss of the oxygen molecules.
Click to expand...

So, it seems to be mediated by hyrdrogen ions rather than pressure. Or is the link wrong?


Anyway, all that has nothing to do with why the bond is bent.
 
Weeellll, to nitpick, the bond isnt bent as such, just angled oddly.
Second, the H ions obviously mediate it, but they are responding to a change in Ph.

And note how there are slightly different ways of looking at it depending upon your specialisation. Compare Electricfetus' with mine or the elmhurst.edu link about proteins.

OK, reading further in my textbook, the increase in hydrogen ions is due to the reaction:
CO2 + H2O <reversible arrows> HCO3- + H+
Ie CO2 is released in the muscles, and is removed in the form of HCO3 ions, which are soluble in water. THis leaves excess H+, which is picked up by the protein chain of the deoxyhaemoglobin. Which is what the link says above, but I thought this might help explain it further.

As for the mode of bonding of O2 to Fe, it is still apparently not clear whether i is end on linear Fe-O-O, or bent /O
Fe-O
Or side on /O
Fe I
\O
 
invert_nexus,

Hey I'm reading out of the biochemistry book here it clearly shows (even in charts) a relationship of hemoglobin saturation to Torrs (pressure) but yes salinity, BPG and pH levels effect hemoglobin saturation as well, but not nearly as much as pressure. Venous pressure is ~26 Torr and Arterial Pressure is ~100 Torr, hemoglobin saturation is ~50% by ~95% consecutively. Lower pH drops hemoglobin saturation: so more oxygen is released in more active tissues that are producing carbonic and lactic acid.

What your focusing (and that site) is on how the C terminal changes from deoxygenated to oxygenated hemoglobin, two groups here become partially deprotenated, this is an effect of hemoglobin oxygenation not a cause.
 
Last edited:
guthrie said:
As for the mode of bonding of O2 to Fe, it is still apparently not clear whether i is end on linear Fe-O-O, or bent /O
Fe-O
Or side on /O
Fe I
\O
Click to expand...

It looks more or less like this:
------------O
----------//
--------- O
----------|
----------Fe
 
Ah ha, thanks. I'm assuming that is more up to date info than in my book.
 
It's not bent. The bond Fe2+-O is penpendicular to the Fe. The rest of oxygen is bent (see Nasor's picture above). For example CO with it's nonbonding el. pair is linear, but can't bind penpendicular to Fe because of steric hindrance from distal histidine. That's why CO has only 200-times higher affinity than O2 (instead of 10000 higher in steric-free hem)
 
You must log in or register to reply here.
Back
Top