Heme Prosthetic Group - Online Tutor, Practice Problems & Exam Prep

The heme prosthetic group, crucial for myoglobin and hemoglobin, consists of a flat, planar structure with an iron (Fe²⁺) atom at its center, allowing reversible oxygen binding. This interaction is facilitated by non-covalent bonds with nitrogen atoms and histidine residues. Oxygen binding induces conformational changes in hemoglobin, promoting its active R state through positive cooperativity. In contrast, carbon monoxide binds more strongly to heme, posing a significant toxicity risk. Understanding these interactions is essential for grasping oxygen transport mechanisms in biological systems.

Heme Prosthetic Group

In this video, we're going to begin our discussion on the heme prosthetic group that both myoglobin and hemoglobin have. Now, before we get into all of the nitty-gritty details on the heme prosthetic group, let's first back up and give you guys some context as to why exactly this heme prosthetic group is so important to myoglobin and hemoglobin anyways.

And so, in order to be able to understand why this heme prosthetic group is so important, we first need to address the fact that amino acids themselves actually lack affinity to oxygen. What this means is that if myoglobin and hemoglobin only consisted of amino acids and were just straight simple proteins, then myoglobin and hemoglobin would lack an affinity to oxygen since amino acids lack an affinity to oxygen. But we already know that both myoglobin and hemoglobin's biological roles involve binding to oxygen and so they need to have an affinity to oxygen. And so, myoglobin and hemoglobin actually rely and depend directly on the prosthetic group called heme in order to bind to oxygen and perform their biological roles. Unlike amino acids, which lack an affinity to oxygen, iron, specifically iron^{2+}, can actually reversibly bind oxygen in just the way that allows myoglobin and hemoglobin to perform their biological roles.

If iron is able to reversibly bind oxygen, why can't the iron Fe^{2+} all by itself, iron all by itself, be a replacement for the biological roles of myoglobin and hemoglobin? Well, it turns out that we can't just use iron atoms all by themselves to replace myoglobin and hemoglobin's biological roles because unbound, free iron is actually really reactive and it's so reactive that it will actually turn oxygen into free radicals. And that really leads to our first problem, the fact that iron all by itself is not going to be a suitable replacement for myoglobin and hemoglobin's role. And again, this is because free iron, essentially iron all by itself, iron atoms all by themselves, is going to lead to the generation of free radicals, which will create radical chain reactions, which we know from our previous courses can actually damage the cell or potentially even kill the cell. Iron only, again, is not going to be a suitable replacement for myoglobin and hemoglobin.

So, then how about just taking the iron and the rest of the heme prosthetic group and just using these two to replace myoglobin and hemoglobin? Why couldn't we do that? Well, that leads to problem number 2, that the iron in this free heme, which is essentially heme that's not bound to any protein, this iron is still going to be reactive. It's still going to be reactive and so this iron^{2+} is capable of being oxidized into iron^{3+}. And iron^{3+} is a problem because it does not reversibly bind oxygen like iron^{2+} does.

And so again, taking the iron and the heme all by themselves is not going to be a suitable replacement for myoglobin and hemoglobin's biological roles. And so this leads directly into the solution to getting myoglobin and hemoglobin's biological roles and that is the fact that when we combine free iron, the rest of the heme, and the hemoglobin molecule, the iron^{2+} that's found in this protein-bound heme over here is going to be much less reactive and because it's less reactive, it's not going to create free radicals and it's not going to be oxidized into iron^{3+}. And so that means that it remains in the form iron^{2+} when we combine all three of these. And that means that it's capable of reversibly binding oxygen and performing the biological role. And so what we can say is that this indeed is the correct solution to combine these three.

And so now that we have a better idea of why this heme prosthetic group is so important to hemoglobin and myoglobin, we can continue on to talk more details about the heme prosthetic group structure. So, I'll see you guys in our next video.

Heme Prosthetic Group

So now that we know why the heme prosthetic group is so important to both myoglobin and hemoglobin, in this video, we're going to focus on the structure of the heme prosthetic group, which really does remind me of a UFO shape. And that's because UFOs are very flat and planar and disc-shaped, and so is the structure of the heme. Because UFOs and hemes are so flat and planar and disc-shaped, we can actually look at them from completely different angles and get a completely different visual representation. So here we're clearly looking at the top of the UFO, and that's what makes it look like a disc shape, so broad and wide. And so, over here, we're looking at the heme from a similar angle, from the top of the heme. And that's why it looks so broad in this fashion. However, again, we can look at this UFO and this heme from a different angle, and it can look completely different. In our next video, we'll be able to look at the same heme just from a different angle and get a different visual representation. And so, you'll be able to see the same thing in your textbooks and in your class PowerPoints, so it's important to be able to understand how the heme is flat and disc-shaped just like a UFO.

Now, it's also important to note that the heme prosthetic group is mostly a non-polar structure, and so we can see that down below as well, that most of the structure of the heme here actually consists of hydrocarbon chains, and hydrocarbon chains are non-polar. So there are a few polar groups on this heme group, but again, most of the structure is non-polar. And so, because most of the heme structure is non-polar, it's mostly surrounded by non-polar amino acids, when deep within the hemoglobin and myoglobin proteins. It's important to know that this heme prosthetic group, when it attaches to hemoglobin and myoglobin proteins, it mainly attaches via non-covalent interactions. And so, there are no covalent interactions that allow the heme to attach to the hemoglobin and myoglobin proteins. It's mainly non-covalent interactions, such as hydrophobic interactions, between all of these non-polar groups.

Now, what's also important to note is that right in the center of this heme prosthetic group here, what we have is an iron atom, an iron 2+ atom, which is really known as ferrous iron. And so, the ferrous iron or Fe2+, it actually complexes with a planar tetrapyrrole ring system. This is just really a fancy name for what we see in hemoglobin structure down below. So here in the center, what we have is the iron atom and everything else that's surrounding the iron atom is referred to as this tetrapyrrole ring system. Now, tetra again just means four, and so basically what this is saying is that these rings that we see right here are called pyrrole rings. So we have four pyrrole rings in this ring system. And, we already know that it is a planar structure, meaning that it is flat and disc-shaped just like the UFO. And so, the name for this tetrapyrrole ring system is actually protoporphyrin 9, and so that is the name that biochemists gave to this ring system. Together, the ferrous iron, Fe2+, and this protoporphyrin 9 system form the heme prosthetic group. And so, it's important to note here that the heme prosthetic group is really referring to both the iron and the protoporphyrin ring system together. Iron protoporphyrin 9 is an alternative way to symbolize the heme. And so, that might be something good to know for your exams as well because your professors might just refer to the heme as iron protoporphyrin 9.

And so, now that we've covered the basics of the structure of this heme, in our next video, we'll be able to look at a different visual angle of this heme group. So I'll see you guys in that video.

Heme Prosthetic Group

So in our last lesson video, we already mentioned that the heme prosthetic group kind of resembles a UFO because they're both very flat, planar, and dish-shaped. Just like we can look at a UFO from different angles, we can look at it from the top view, and we can also look at it from the side view, just like we're looking at the side of the UFO over here. The heme is very flat and planar, similar to this UFO, and we can also look at the side of the heme as well. This representation, as well as this representation over here, are both looking at the side view of the heme. Notice that we still have our iron atom right in the center, and branching off the iron, what we have is the rest of the heme prosthetic group. We're not showing all of the atoms here in this representation, but this is a more simplified version.

Now notice over here with this UFO that it is actually abducting this cow right here, and it looks like our little alien dude has popped out of the spaceship and he's saying, "ET phone hem," and that's because of the heme group right here of course, and so, hopefully, all of this will help you guys associate the flat planar disc shape of the UFO with the flat planar structure of the heme. We already know that the heme prosthetic group is responsible for reversible binding of oxygen molecules. What I want you guys to know is that the oxygen atom actually binds to the iron atom above the plane of the heme.

Notice down below that our heme prosthetic group is this flat structure right here. Then above the plane of the heme, notice we have the oxygen gas molecule that's bound non-covalently. If we were to show that over here on the right, we would have the oxygen atom bound again above the plane of the heme, above the UFO. The oxygen is able to bind to the iron atom without reacting to form free radicals because it is also bound to this hemoglobin molecule. Notice that the iron atom in the center is bound to the hemoglobin molecule.

The next point that I want to make is that carbon monoxide is an extremely toxic compound for many different reasons. However, one of the reasons that carbon monoxide or CO is so toxic is that carbon monoxide can actually bind to the heme stronger than oxygen. Because carbon monoxide binds to the heme stronger than oxygen, it can outcompete oxygen for binding to the iron atom. If carbon monoxide is bound to the iron atom, then oxygen is not capable of binding. You could almost think of the carbon monoxide as acting like a competitive inhibitor and just blocking the site for oxygen binding. Over here, we're showing the heme prosthetic group from the side, bound to carbon monoxide. The point we want to make here is that carbon monoxide or CO will actually bind to the heme, the iron in the heme, much stronger than the oxygen gas molecule, making the carbon monoxide extremely toxic.

Now that we've covered the visual representations of the heme prosthetic group, we'll be able to show even more visual representations of the heme and talk more details about it as we continue forward in our course. So I'll see you guys in our next video.

Heme Prosthetic Group

So now that we know a little bit about the structure of the heme prosthetic group, in this video we're going to focus on the interactions of the iron atom in the hemeprosthetic group. And so taking a look at our image down below, notice we're looking at a hemoglobin molecule. And more specifically, we're zooming in on one of hemoglobin's heme prosthetic groups. And so it's important to know that the iron atom of the protein bound heme can actually form a total of 6 non-covalent bonds. 4 of those 6 non-covalent bonds are formed with the nitrogen atoms of the protoporphyrin 9 system, and because these 4 bonds are formed with the protoporphyrin 9 system, they're going to be found in the same exact plane as the heme prosthetic group. And so taking a look at our image down below, notice that we have the iron 2+ atom right in the middle of the heme prosthetic group. And this iron atom is forming 4 non-covalent bonds with the nitrogen atoms of the protoporphyrin 9 system. And these 4 bonds are going to be found in the same exact plane as the heme prosthetic group. Now one bond, one of these 6 non-covalent bonds is going to be formed with what's known as a proximal histidine residue. And so proximal just means that it's going to be in close proximity to the iron. And so this one bond with the proximal histidine residue is going to be found below the plane of the heme prosthetic group, essentially going below the ufospaceship if you will. And so notice here we have the iron atom and going below the heme prosthetic group, we have what's known as the proximal histidine residue. And so we can label this histidine here as the proximal histidine residue because it's in close proximity to the iron atom. And so this final non-covalent bond, we've got a total of 5 so far. The final one is going to be a bond with an oxygen atom, and that oxygen atom is going to bind above the plane of the heme prosthetic group as we already know. And so notice over here, what we have is a heme prosthetic group that is not bonded to oxygen. And so right now, this iron atom only has 5 total non-covalent bonds. 4 with the nitrogen atoms and one with the proximal histidine. However, as soon as oxygen comes into play, we can get the oxygenated form and so notice that it maintains the same exact 5 non-covalent bonds but now it has an additional non-covalent bond going up with the oxygen atom. And so you can see the exact 6 non-covalent bonds that the iron forms, right here on this side of the image. Now what you'll also notice is that there is another histidine, that is part of the hemoglobin molecule. So remember that this heme prosthetic group is embedded deep within the hemoglobin protein and so it's surrounded by a lot of hemoglobin protein. And so, here, we're not showing this particular histidine, but it is present. And it really only comes into play when the oxygen is bound, which is why we're only showing it over here on the right. And so this particular histidine is forming a bit further away from the iron atom and so it's not going to be proximal. It's actually going to be distal and that's because it's distant. So distal is for distant. And again, this histidine is distant, more distant from the iron atom. And so down below, you can see that we're saying that a distal histidine residue is actually going to be responsible for stabilizing the oxygen atom in the oxygen-bound heme, and it does so via a hydrogen bond which is another non-covalent bond. So this bond right here is a hydrogen bond. And so, this hydrogen bond here is so important because what it does is it prevents the conversion of the iron 2+ atom, which is right here, which we know can reversibly bind oxygen very well. And it prevents the conversion of this Iron 2+ to the Iron 3+. And so we know that the Iron 3+ is not going to be able to revers

When O₂ binds to a heme group, the two bonds of Fe²⁺ that are not planar with the heme are occupied by:

• A. One O₂ molecule and one Ser amino acid atom.
• B. One O₂ molecule and one His amino acid atom.
• C. One O₂ molecule and a nitrogen atom of the heme.
• D. Two O₂ molecules.

Heme Prosthetic Group

So like hemoglobin, myoglobin's heme group forms very similar iron interactions. And so we can see that down below. We can see that we have the heme prosthetic group right here, which is, of course, embedded deep within the myoglobin protein. And if we zoom in on this even further, what we'll see is, we've got the hemoglobin protein here, which is very similar to, like, an alien UFO spaceship. And so in the middle here, we have the iron ²⁺ atom, which is going to be forming its 6 non-covalent interactions. We know that 4 of those non-covalent interactions are going to be in the same plane as the heme prosthetic group, and then it'll have one interaction going below with a histidine residue, and the iron is directly binding to this histidine residue non-covalently. And so, that was what makes this the proximal histidine residue because it's in close proximity to the iron atom. And then, of course, you can see that we've got the oxygen atom right here, the O₂ right here. And, of course, what you'll also notice is that we've got another histidine residue that's part of the myoglobin that is binding to the oxygen atom and it's not binding to the iron atom. And so it's further away from the iron atom. So, we can say that it is the distal or the distant histidine. And so, these are going to be very similar interactions to what we talked about in our last lesson video. So, now that we know that, we can move on to our next video.

The distal histidine residue in myoglobin acts to:

• A. Prevent oxidation of the heme Fe²⁺.
• B. Lower the relative affinity for CO.
• C. Assist in the binding of O₂.
• D. Prevent release of N₂.
• E. a & b.
• F. a, b & c.
• G. All the above are true.

Heme Prosthetic Group

In this video, we're going to talk about how oxygen binding to the heme prosthetic group actually causes hemoglobin's conformational changes. And so recall from our previous lesson videos, we said that hemoglobin itself is actually an allosteric protein. And so of course what this means is that it has its inactive T state that inefficiently binds to ligand, and it also has its active R state that efficiently binds to ligand. And so what's important to note here is that the binding of oxygen gas specifically to the heme prosthetic group actually causes a very slight and subtle change in the heme prosthetic group's conformation.

And so, if we take a look down below at our image, notice on the left-hand side over here, what we have is deoxygenated hemoglobin, and we can tell it's deoxygenated because the oxygen gas molecule is not bound above the plane of the heme. And so we've got the heme group represented right here and then, of course, below what we have is hemoglobin's proximal histidine residue. And we know that this is the proximal histidine residue because it's in close proximity to the iron atom and it's bound directly to the iron atom. And so, of course, what we're showing here is oxygen binding to the heme binding to the heme prosthetic group. And on the right, what we have is oxygenated hemoglobin.

And so what's important to note here is that the deoxygenated hemoglobin over here on the left, the iron atom is actually quite large and it's so large that it actually does not fit into the hole that's in the center of the heme group up here. And so what this means is that the plane of the heme, which is right here, is going to be slightly above the iron atom. And the iron atom is going to be slightly below the plane of the heme because it's so large when it's not bound to any oxygen. And so what's important to note is that upon binding to oxygen gas, the iron atom of the heme prosthetic group actually becomes significantly smaller.

And so what this allows is it allows for the iron atom to shift up into the plane of the heme. And so notice that upon oxygen binding, the iron atom in the center becomes significantly smaller. And because it becomes significantly smaller, the iron atom actually shifts up into the heme plane upon oxygen binding. And so now, you can see that everything is in the same plane whereas over here, we had the iron below the plane.

So there is a very subtle and a very slight conformational change in the heme's structure. And so really, this slight conformational change in the heme's structure ultimately causes other hemoglobin protein subunits to change conformations as well. Specifically, it causes them to change conformation from the inactive T state towards the active R state. And so, of course, we know this is a sign of positive cooperativity. And so this is positive cooperativity because it's promoting the R state and promoting additional binding of oxygen to other hemoglobin subunits.

And so in our next topic, we'll be able to talk more about this cooperativity that takes place between hemoglobin subunits. And also, I want to take this time to point out that myoglobin, because it only has one single subunit, does not display any cooperativity at all. It's only hemoglobin, which is the allosteric protein, that displays this positive cooperativity. So this here concludes our lesson, and again, the main takeaway is that oxygen binding to the heme group causes hemoglobin's conformational changes, leading to positive cooperativity in hemoglobin subunits. And so I'll see you guys in our next video.

In hemoglobin, the equilibrium transition from T state to R state is triggered by:

• A. Fe²⁺ binding.
• B. Heme binding.
• C. Oxygen binding.
• D. Protease cleavage.

Here’s what students ask on this topic:

Why is the heme prosthetic group important for myoglobin and hemoglobin?

The heme prosthetic group is crucial for myoglobin and hemoglobin because it enables these proteins to bind oxygen, which is essential for their biological roles. Amino acids alone lack the affinity for oxygen, but the iron (Fe²⁺) in the heme group can reversibly bind oxygen. This binding is necessary for oxygen transport and storage in the body. Without the heme group, myoglobin and hemoglobin would be unable to perform their functions, as free iron is too reactive and can generate harmful free radicals. The heme group stabilizes the iron, allowing it to bind oxygen safely and effectively.

What is the structure of the heme prosthetic group?

The heme prosthetic group has a flat, planar, disc-shaped structure, similar to a UFO. It consists of a central iron (Fe²⁺) atom surrounded by a planar tetrapyrrole ring system called protoporphyrin IX. This ring system includes four pyrrole rings connected by methine bridges. The heme group is mostly non-polar, with hydrocarbon chains making up the majority of its structure, and it attaches to proteins like hemoglobin and myoglobin via non-covalent interactions, primarily hydrophobic interactions. The iron atom in the center is crucial for binding oxygen molecules.

How does oxygen binding to the heme group cause conformational changes in hemoglobin?

Oxygen binding to the heme group induces conformational changes in hemoglobin by altering the size and position of the iron (Fe²⁺) atom. In deoxygenated hemoglobin, the iron atom is too large to fit into the plane of the heme group. Upon oxygen binding, the iron atom becomes smaller and shifts into the plane of the heme. This subtle change triggers a shift in hemoglobin's structure from the inactive T state to the active R state, promoting further oxygen binding through positive cooperativity. This mechanism enhances hemoglobin's efficiency in oxygen transport.

What are the interactions of the iron atom in the heme prosthetic group?

The iron (Fe²⁺) atom in the heme prosthetic group forms six non-covalent bonds. Four of these bonds are with the nitrogen atoms of the protoporphyrin IX system, lying in the same plane as the heme. One bond is with a proximal histidine residue below the plane, and the final bond is with an oxygen molecule above the plane. Additionally, a distal histidine residue stabilizes the bound oxygen via a hydrogen bond, preventing the conversion of Fe²⁺ to Fe³⁺ and reducing carbon monoxide's binding affinity, thus protecting the heme's function.

Why is carbon monoxide (CO) toxic in relation to the heme group?

Carbon monoxide (CO) is toxic because it binds to the iron (Fe²⁺) in the heme group much more strongly than oxygen (O₂). This strong binding outcompetes oxygen, preventing it from binding to the heme and thus inhibiting oxygen transport in the body. CO acts like a competitive inhibitor, blocking the site for oxygen binding. This can lead to severe tissue hypoxia and potentially fatal outcomes. The presence of a distal histidine residue in hemoglobin helps reduce CO's binding affinity, but it is not enough to completely prevent CO toxicity.