Biochemistry Glycoconjugates

Hello and welcome back to Educator.com, and welcome back to Biochemistry.0000

In the last lesson, we talked about polysaccharides.0004

We are going to continue our discussion of polysaccharides, and talk about something called glycoconjugates.0007

These are polysaccharides that are attached to proteins and lipids.0013

Let's just go ahead and jump in, get started.0022

OK, let's make sure we have...let's start off with black here.0026

In addition to their structural and fuel storage roles - actually, I do not think I will use the word "roles", I think I will use the word "capacities" - oligo and polysacchs - excuse me - they also carry information.0031

OK, let's go over here; they also carry information.0087

In other words, in this particular case, they are involved - as we mentioned in the previous lesson - in cell to cell and cell extracellular matrix interactions.0093

In other words, they are involved in recognition.0122

OK, in these cases, the carbohydrate, oligopolysaccharide, the carbohydrate is often joined to a protein or a lipid.0125

Lipid is just a fancy word for fat, and we are going to be discussing lipids in great detail very, very soon.0160

OK, let's talk about these things called proteoglycans.0167

Let me go to blue here, and let me see.0171

Is proteoglycan like a protein?0175

Yes, that is fine; alright, proteoglycan.0177

Our first class of glycoconjugates are these things called proteoglycans.0185

OK, they are cell surface and extracellular.0192

Extracellular means that they are just proteins that are not attached to the cell; they are actually proteins that are floating around in the cytosol.0202

That is all that means- proteins with one or more glycosaminoglycans, one or more Gags attached.0207

OK, now, these things called proteoglycans, they are the carbohydrates, but they are attached to cell surface proteins or they are attached to free proteins, secreted proteins, proteins that have been created and sent outside of the cell to sort of wander around in the matrix or wherever it is that they wander around, proteins with one or more glycosaminoglycans attached.0227

What is important here is the attachment to the protein is an actual glycosaminoglycan, and you remember from the last lesson that the glycosaminoglycan is this particular polysaccharide that has alternating, it is a linear polymer.0254

It is not branched; it is linear, but it alternates A-B, A-B, A-B with a certain collection of monomers, those monomers generally being N-acetylglucosamine or N-acetylgalactosamine and the other monomer being, more often than not, a glucuronic acid or an iduronic acid.0269

Now, other things can show up; it is not a problem, but the majority of the glycosaminoglycans are going to be those.0289

So, when that particular arrangement of polysaccharide is attached to a protein, we call that glycoconjugate; the whole thing, it is called a proteoglycan- that is all this is.0296

The carbohydrate in a proteoglycan tends to dominate the structure, and that is where the biological activity is.0306

The protein just happens to be a point of attachment.0316

OK, another family of glycoconjugate is something called a glycoprotein.0320

I know, it is kind of interesting, isn't it?0328

Glycoprotein, notice, here, proteo is first, glycan is second; here, glyco is first, protein is second.0330

Now, these are proteins with one or more oligosaccharides covalently attached, and they are also covalently attached here.0337

They can be covalently or electrostatically, but here, they are covalently attached.0364

Now, the carbohydrate portion is generally more varied in the sense that there is a greater collection of monomers to choose from, that the oligosaccharide is made of, is more varied and complex than the glycosaminoglycans on the proteoglycan, the glycosaminoglycan chains on the proteoglycans.0370

If you see a protein, and it has some carbohydrate attached, if the carbohydrate attached happens to be a glycosaminoglycan, we are talking about a proteoglycan- the whole thing.0422

If it tends to have some oligosaccharide or polysaccharide attached, but it is a lot more complex and it has branching, that is a glycoprotein.0430

That is the difference between the two; I will actually write that out in just a second.0440

Let me go ahead and just run through the list here of glycoconjugates.0445

We have proteoglycans, glycoproteins, and now, we have something called a glycolipid.0450

Now, this is just lipids in the cell membrane that have oligosaccharides attached- that is it.0461

In this particular case, the carbohydrate, the oligosaccharide, the polysaccharide, is attached to a fat, not a protein - that is it - covalently linked.0486

OK, now, proteoglycan versus glycoprotein.0496

I know this is good.0505

Now, what is the difference, proteoglycan, glycoprotein?0508

Here is the difference.0510

Proteoglycan, it has a linear glycosaminoglycan attached- that is the difference.0512

The attachment to the protein is some linear glycosaminoglycan, and we know that a glycosaminoglycan is a heteropolysaccharide.0524

It is linear, has no branching; and it consists of alternating monomers, A-B, A-B, A-B- whatever those monomers happen to be.0533

OK, linear Gag attached, and, of course, the Gags are repeating disacch units - that is how you tell - whereas a glycoprotein, it has various oligos attached, different monomers, linear, branched, all kinds of crazy things, any arrangement, high binding specificity.0542

Now, we said that these oligosaccharides attached to proteins that are on the cell surface are floating around, they serve recognition purposes.0594

Well, yes, proteoglycans are involved in recognition; glycoproteins are involved in recognition.0606

Proteoglycans are involved in sort of a global recognition - attached here, attached there.0612

Because these tend to be smaller, more complex, they have a higher binding specificity.0620

They bind specific things at specific points, whereas a proteoglycan might have some glycosaminoglycan attached; and maybe, it is sort of attached at 15 or 16 different points, just sort of like, it is attached here, attached here, attached here, sort of like a claw, whereas these glycoproteins are attached in one location.0626

So, these oligosaccharides tend to be much smaller, and they have very high binding specificity- that is the thing.0648

These glycoproteins are the ones that are involved in your body's immune response.0656

The immune cells that your body sends out to attack invaders recognize these glycoproteins on the cell surface of the bacteria and viruses and things like that.0664

OK, let's take a look at a drawing here, and OK.0675

This is a cell surface; a cell is a lipid bilayer, so that is this thing right here in blue.0681

OK, we are not going to worry about that; let's just sort of take a look and see some of these things.0690

Now, notice this particular protein here; this particular protein looks like it has a couple of things attached, so it looks linear.0697

This could be a proteoglycan; I will just say PG.0708

This could be a proteoglycan.0711

This over here, this is a membrane bound protein; part of it is in the membrane.0714

Part of it is inside the cell; part of it is outside the cell.0720

This is inside the cell here; this is outside the cell, and it has this oligosaccharide attached.0723

Notice, this is not a linear oligosaccharide; this is, it branches here.0730

It branches there, and it branches there.0735

This one is a glycoprotein- that is it.0737

That is how you tell; I mean unless you do a particular analysis, there is no way to actually tell, but this pretty much gives it away.0741

If you have some extensive branching, you are pretty much looking at something which is a glycoprotein.0749

It is going to be a very specific binding site.0754

Let's see, over here, there is another in an integral protein.0757

Integral means it is part of the cell membrane.0761

There is a part of the protein that extends inside; there is a part that extends outside, and again, we have a linear.0765

Now, this could be a glycoprotein; it just depends on what the identity of this oligosaccharide is.0770

If it happens to be a glycosaminoglycan, let's say something like chondroitin-4-sulfate, we know that this whole thing, the protein and the oligosaccharide, is a proteoglycan.0775

If it happens to be just some collection of monomers - N-acetylglucosamine, N-acetylgalactosamine, maybe a mannose, maybe a galactose, something like that - then we know we are looking at a glycoprotein.0786

It serves a more specific type of recognition site- that is all it is, and this is what it is going to look like.0800

You see, all of these proteins, they have little oligosaccharides.0807

Your cells are covered in this stuff; bacteria is covered in this stuff.0811

That is how things get recognized; in this particular case, glycoprotein, proteoglycan, I just wanted you to see what this looks like.0815

Now, over here, we have this glycolipid.0825

Here, we have a lipid molecule, some fat; and again, we will be talking about lipids specifically, but here, you have an oligosaccharide that is attached to a fat.0829

It is not attached to a protein, not a proteoglycan, not a glycoprotein, but it is in the third class; it is a glycolipid- that is it.0838

It just means it has a sugar that is attached to some fat- that is it.0846

We will return to this a little bit later in the lesson when we get into a little bit more detail about proteoglycans and glycoproteins.0851

OK, let's talk about proteoglycans first, and let's talk about their common structure.0857

Proteoglycans are alright, proteoglycan common structure, and by common structure in this particular case, what I am going to discuss is the point of attachment to a protein.0869

In this case, we said that this was our proteoglycan, so we are going to be talking about - you know, I should do this in black, this right there - how it is actually attached to the protein.0894

Well, here is how it is attached to the protein; let's go ahead, for our example.0905

I wonder if I should do this on the next page.0912

Yes, that is fine; I should have enough room here.0916

Let's go ahead and actually do a chondroitin-4-sulfate.0917

OK, chondroitin-4-sulfate, it is a glycosaminoglycan; it is linear, and its particular monomers are glucuronic acid and N-acetylgalactosamine, and I am going to write that down in just a second.0930

So, I am not going to draw these structures; I am just going to write their names connected.0949

I have got a GlcA; I have got it connected to a GalNAc- that is the N-acetylgalactosamine - and I am going to write one more GlcA, right?0953

So, we have alternating A-B, A-B, A-B, and this is going to be connected to a galactose, which is going to be connected to a galactose, which is going to be connected to a xylose sugar.0967

Remember, xylose is a 5-carbon sugar; galactose is a 6-carbon sugar, and this happens to be connected to a serine residue, which is part of the polypeptide, which makes up the protein.0980

And, that is the term Gly, Hex, Gly; and, of course, the polypeptide continues on in this direction.0999

This is going to be the N-terminus.1008

Now, when it is attached to a serine residue, what tends to be attached to the serine is another glycine, some other amino acid and some other glycine.1011

In general, this is what we tend to find more often at this point of attachment, and, of course, this polymer goes on that way, the polypeptide, and this is the C-terminus.1023

OK, this tends to be the arrangement.1033

Right there, at the protein's surface, there is some serine, glycine, some other amino acid and glycine, this arrangement, and then attached to the serine, you will have a xylose sugar, a galactose, a galactose, and then, of course, you will have your molecule.1035

Here is your molecule of your chondroitin-4-sulfate.1049

This is our chondroitin-4-sulfate, and this is our trisaccharide linker that links the protein, the amino acid serine, to our glycosaminoglycan, which is the chondroitin-4-sulfate.1058

This is our trisaccharide connector.1080

OK, let's see; all these crazy words floating around.1087

OK, and let's do this one in red.1097

This right here, this glycosidic bond is going to be beta-(1,3).1102

The anomeric carbon of the glucuronic acid is connected to galactose at its no. 3 hydroxy on the no. 3 carbon.1107

This connection right here is a beta-(1,3) glycosidic bond.1118

Now, let's go ahead and draw out serine just so you see what serine looks like as a reminder.1124

We have NCC; serine has a CH₂, and it has that, and, of course, this is H.1132