O2/CO2 and Myoglobin and Hemoglobin

[anoxredcat]

Background info I know:
O2 binds to hemoglobin better than myoglobin because of cooperative binding>non-cooperative binding and hemoglobin's high sensitivity to PO2.

1. CO binding to free heme has higher affinity than CO binding to myoglobin heme. Why? Maybe I'm confused what free heme is...

2. Within myoglobin, O2 binds to Fe2+ at an angle relative to the porphyrin ring (preferred conformation), but due to the distal His, CO binds perpendicularly to the plane of the porphyrin ring (not preferred)-> decreasing CO binding affinity. But then why overall, CO binds to the heme better than O2?
Is it because when O2 binds Fe2+ stays Fe2+
And when CO binds Fe2+ turns into Fe3+, kind of locking CO in place?

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[aldol16]

O2 binds to hemoglobin better than myoglobin because of cooperative binding>non-cooperative binding and hemoglobin's high sensitivity to PO2.

At lower O2 concentrations, O2 actually binds to myoglobin way better. Myoglobin has a very high affinity for O2.

1. CO binding to free heme has higher affinity than CO binding to myoglobin heme. Why? Maybe I'm confused what free heme is...

Free heme is an iron porphyrin without the protein around it. So basically, no steric constraints to binding (as you say, steric constraints is why the myoglobin/hemoglobin affinity for CO is lower than what it should be (though still 200 times higher than for O2).

2. Within myoglobin, O2 binds to Fe2+ at an angle relative to the porphyrin ring (preferred conformation), but due to the distal His, CO binds perpendicularly to the plane of the porphyrin ring (not preferred)-> decreasing CO binding affinity. But then why overall, CO binds to the heme better than O2?

You're standing at ground level. Your friend is on the roof of a 200 floor skyscraper. He then takes an elevator to the 10th floor. He has cut his potential energy by a factor of 20. But he's still got 10 times more potential energy than you.

And when CO binds Fe2+ turns into Fe3+, kind of locking CO in place?

CO is an L-type ligand using neutral ligand formalism so it does not oxidize iron upon binding.

 

[anoxredcat]

My reply/questions in green!

At lower O2 concentrations, O2 actually binds to myoglobin way better. Myoglobin has a very high affinity for O2.
So maybe you can debunk this for me. I was always taught that myoglobin's saturation curve is hyperbolic (non-cooperative) and hemoglobin's is sigmoidal (cooperative). Since cooperative binding allows for that high sensitivity of PO2, hemoglobin automatically wins (more saturated O2 within the same range compared to myoglobin).

So maybe its the wording of "at low O2 concentrations?" Does this have to do with something regarding the fight or flight response, where the body is willing to supply oxygen to more important things? Or is this a too far stretch.


Free heme is an iron porphyrin without the protein around it. So basically, no steric constraints to binding (as you say, steric constraints is why the myoglobin/hemoglobin affinity for CO is lower than what it should be (though still 200 times higher than for O2).
I'm assuming this is why carbon monoxide poisoning is so deadly...
so in my picture, I asked a few more questions
1. is the bent shape of CO more preferred
2. If the question were "Why does CO bind with more affinity to free heme than to myglobin?" My answer would be because in free heme there are no proteins to strain CO into its non-preferred state (perpendicular). Any more reasons? Or how would you answer that questions?

CO is an L-type ligand using neutral ligand formalism so it does not oxidize iron upon binding.
So then I read somewhere that Fe is oxidized when something binds. This isn't O2 is it?

Thanks @aldol16 , you're a serious mvp.

 

[aldol16]

1) It's a general trend, not specific to fight-or-flight. Hemoglobin is the primary oxygen transporter in the body. So it'll pick up oxygen in the lungs (where it's fractional saturation approaches 100%) and then goes to the tissues and muscles, where it "drops off" the oxygen. In order for it to drop off the oxygen, it must lower its affinity for oxygen. That's where the sigmoid curve comes in handy. In the muscles, the O2 concentration is low relative to the lungs. So hemoglobin's affinity for oxygen decreases and it drops off the oxygen. Myoglobin affinity for O2 must necessarily be higher than hemoglobin's when hemoglobin is near the muscles because myoglobin must "pick up" that O2 from hemoglobin. It's kind of like how an infant's hemoglobin must have a higher affinity for oxygen than the mother's.

2) No! The point is that the bent shape of CO binding is not preferred! Or else we would all die of CO poisoning at much lower CO levels. Think about it. The CO in carbon is sp hybridized. That means it must bind linearly.

3) If the question was "Why does CO bind free heme with greater affinity than myo/hemo-globin?" the answer would be that in free heme, the CO can bind linearly just fine since there are no steric constraints. In the protein, there are steric constraints that only allows binding in the bent shape, which CO does not like because it's sp hybridized.

4) Fe oxidation state is a bit more complicated. For the purposes of the MCAT, I suppose you could memorize Fe(III). The problem is that molecular oxygen can bind metals in two modes - so-called eta-1 or eta-2. Now, remember that ground state oxygen is not a singlet but rather a triplet - it has two parallel electrons in pi anti-bonding orbitals. Basically, you can imagine it as a di-radical, with a radical at each oxygen. So it can either bind to iron with one electron, oxidizing the iron by one electron, or bind to iron with both oxygens, oxidizing the iron by two electrons. According to experiment, it's likely the former. Iron in heme is 2+ oxidized and once it binds oxygen, it becomes 3+ oxidized, generating a superoxide anion.

There are still people who don't believe that this is the case because of the observed properties of the di-oxo-metal complex, but I suppose this should be sufficient for the purposes of the MCAT.

The idea to take away is that CO doesn't oxidize the iron. C is triply bonded to O, giving a formal charge of -1 on the C and +1 on the O. According to neutral ligand formalism, C must then bring in both electrons when it coordinates the iron (as opposed to oxygen's one) and iron doesn't need to "give up" any of its own electrons.

 

[anoxredcat]

Thank you @aldol16 . That seriously helps. Its a little scary to be applying for med school in the same pool as you (I think). Best of luck to you! 🙂

 

[aldol16]

Ah, it's just because I'm a chemist. I'm a terrible biologist.