Biochemistry Membrane Lipids, Part 2

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

Today, we are going to continue our discussion of membrane lipids by discussing the other classes that we did not discuss in the previous lesson.0004

Let's get started.0009

OK, now, I know that I mentioned 5 classes, and one of those classes was going to be the tetraether lipids.0013

I have decided actually not to discuss those, no particular reason why.0020

You are welcome to look them up in your book; it should be no more than about 5-minute reading.0025

I decided to actually move on to what I consider a little bit more important.0030

The next class I am going to talk about are going to be the sphingolipids.0036

Now, the sphingolipids are characterized, instead of glycerol, these sphingolipids...let me start again.0047

Instead of glycerol, this thing called sphingosine forms the backbone of these sphingolipids to which various groups are attached.0072

OK, let's go ahead and draw the sphingosine structure; I am not doing very well, at all, with spelling today.0102

OK, we have got, yes, that is fine; I will go ahead and do it here.0120

C, C, C, so, we have an OH, and then, we have an NH₂; and then we have an OH, and then we have got C, double bond C.0126

Let me go ahead and put the Hs in here.0140

Let's see, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12; let me see.0145

I have got 1, 2, 1, 2, 3, 4, 5, 6, and yes; there we go.0160

This is sphingosine.0167

Now, what is important to notice is that one of the nonpolar chains is part of the sphingosine, itself.0172

On some sense, it is kind of like the glycerol; I mean you have the OH, and you have the OH, but it is not the OH that is attached.0198

It is actually directly attached, the 1 and the 2 carbon in alkene linkage; and then, of course, you have this other set.0205

You have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 carbons there.0212

This basic structure is sphingosine and to this, so this will always be the same.0221

This is invariable; it is the attachments that go here and here that changes everything.0229

OK, now, when a fatty acid is attached to the nitrogen in amide linkage or an amide linkage - I actually prefer to say amide, myself - in other words, when a fatty acid is attached to that - go back to black - the compound is called a ceramide or a ceramide.0235

Let's go ahead and draw that really quickly.0288

We have C, C, C; so , if I have NH, O, and some R1 group, and, of course, here, we have - let me see - I will do (CH₂)12, and just write it as CH₃, instead of doing the squiggles like that, OH, and, of course, we have our OH.0292

This is a ceramide where this can be variable.0320

And again, notice, this top structure right there, it is the same; that is the sphingosine.0328

This basic structure right here, that is going to be the sphingosine.0337

When a particular fatty acid is attached to the nitrogen, and this is your amide linkage instead of an ester, instead of this being an oxygen, this is a nitrogen, it is called an amide, carbonyl.0346

Now, let's go ahead and talk about the subclasses of the sphingolipids.0361

We have these membrane lipids, and one of the classes is the sphingolipid.0375

Among the sphingolipids, there are subclasses; so now, we are going to divide it up some more.0383

These are derived from the ceramides.0391

In other words, in the case of these particular subclasses that we are going to discuss, they are always going to have the sphingosine.0402

They are always going to have some fatty acid attached in amide linkage to the amine group, and then there is going to be something else that is going to be attached here.0407

They are derived from the ceramides and differ in what is attached to the no. 1 carbon.0415

Let's go ahead and call this our no. 1 carbon.0434

OK, the first is something called the sphingomyelins.0440

The second is something called the neutral glycolipids.0451

Then, no. 3, we have something called the gangliosides.0461

Oops, write it a little bit better.0468

OK, the first one we are going to be talking about - I will go ahead and go to red - we are going to be talking about the sphingomyelins.0474

Now, these contain phosphocholine or phosphoethanolamine - just like the glycerophospholipids - as the head group.0485

OK, let's go ahead and do an example of this; let's go ahead and draw it all out very carefully.0520

We have C, C and C; we have C, double bond C.0527

We have a CH₂ group; we have 12 of them, and then - excuse me - we have a CH₃ group.0534

We have our OH.0542

OK, we have our nitrogen; we have our amide linkage.0547

I will go ahead and just put R1 for whatever fatty acid happens to have reacted, and I will go ahead and do an O here.0550

And now, it says there is a phospho group, so the sphingomyelins, they do contain phosphate just like the glycerophospholipids.0560

A glycerophospholipid and a sphingolipid, they are both phospholipids; they both contain phosphate.0570

Go ahead and do that, and we said it was choline, so we have 2 Cs.0578

We have a nitrogen, and let me go ahead and actually draw in my CH₃ groups; and let's look out for charge here.0584

We have a positive there; we have a negative there.0592

This, right there, that is our choline group; and again, it could be ethanolamine- that is it.0597

This is a sphingomyelin; it happens to have a phosphate group, a choline or an ethanolamine right there on the left.0608

This is the head group, and, of course, we have part of the chain that is always going to be there, that is part of sphingosine backbone.0617

And, of course, this variable fatty acid that is connected to the amine in amide linkage- there you go.0626

This is a sphingomyelin.0635

OK, now, because...you know what, I am not going to actually write all this out; this is going to take too much time.0640

Again, what is interesting here is that phosphate shows up in these sphingomyelins.0650

We had glycerophospholipids; if we want, we can call them sphingophospholipids.0658

That is how I differentiate them; they are phospholipids in general, but one of them the backbone is glycerol, the other one the backbone is sphingosine or in this case the ceramide- that is it.0665

Again, I personally think that there is too much nomenclature in biochemistry.0677

I understand that we have to name this and name that.0683

I have no problems with that, but I think there is definitely a little bit of over classification.0686

I think that if you just draw out the structure and deal with a particular molecule as you deal with it, I think that is enough.0695

Again, as far as you learning this stuff for the first time, it is really, really important not to get bogged down in the classification.0702

Yes, of course, I understand; if you happen to have a teacher that wants to make sure that you can put a particular molecule in a particular class, in a particular subclass, that is fine.0709

It all depends on what it is that your teacher wants, but what is important is that you understand the chemistry, not necessarily the classification scheme.0719

In general, if you stop and sort of look at the name, it will tell you what is going on; but do not get lost in it.0728

You want to be able to see the forest from the trees; it is the chemistry that is important, not these classification schemes.0735

They have always made me crazy, but you know what, that is the nature of the game; we live with it.0740

Anyway, let's go ahead and see if we can move forward here.0745

Now, let's go ahead and talk about the glycosphingolipids.0750

OK, let me see here, yes.0756

OK, we just talked about the sphingomyelins; and now, we are going to be talking about the glycolipids - OK, let me do this in blue - or what I just wrote down as the neutral glycolipids, so glycosphingolipid.0762

OK, now, couple of things, these occur mostly in the outer leaflet of a membrane bilayer; and they have 1 or more, usually not more than about 3 or 4, sugar monomers - I do not want you to think of like 15, it is not going to be like that - attached to the ceramide backbone without a phosphate linkage.0788

That is what is important; in the sphingomyelins, you have this phosphate group that is going to, sort of, be connected to the ceramide, and it is going to be connected to the particular alcohol or whatever it is that is attached.0850

In the case of these glycosphingolipids, the sugar monomers are going to be directly attached without this phosphate intermediary.0865

OK, let's go ahead and...so, we have 2 types.0874

Again, I personally think all of this extra classification is completely unnecessary, and I think it complicates matters.0880

So, I hope that I can make it as clear as possible.0886

I think too much classification really is not a good thing, but the material is presented like this, so we will go with what they have.0893

Our first type is going to be the cerebrosides.0903

There is 1 monomer, and that monomer is either going to be glucose or galactose.0910

You see, the galactose tends to show up in a lot of these, and the other, they are called the globosides; it is exactly what you think it is.0925

They are the ones that have 2 or more monomers, and again, you probably will not see more than 3 or 4.0934

OK, and last bit of information, both are electrically neutral.0943

OK, let's go ahead and take a look at a cerebroside.0956

Let's go ahead and do this one in black.0960

We have C; we have C.0964

We have C, double bond C; I have got my methylene group, 12 of them.0966

I have CH₃; I have my nitrogen.0972

I have my carbon double bond; I will go ahead and put R1, and here, I will go this way.0978

I will go O; I will go that way, maybe not- that is fine.0987

I don't know; it does not really matter.0994

Let's go ahead and let's do it like this; let's go ahead and do O, and let's go like that.0995

How is that?1001

And, we will go ahead and do something like this; let's go OH.1003

Let's go OH; now, let's go ahead and put glucose on there today, CH₂OH.1010

This is a cerebroside.1016

It has 1 monomer of glucose or galactose attached to the ceramide, and this is usually what is going to be variable- that is it.1022

It is called a cerebroside, just happens to be one of the names for it.1030

OK, let's go ahead and do a globoside, and let's use 2 monomers.1034

We have got again our C, our C, our...oops...I think I...oops...you know, I always forget that OH there; my apologies.1040

Yes, it is very, very important to remember that there is that OH there, so let me go ahead and put that in first.1047

That is that, and we have our double bond, yes, and then we have (CH₂)12, CH₃; and you can see how easy it is to get lost here.1053

And, that is N, and C, and R1; let's go ahead and go O.1071

OK, let's go ahead and put 1 monomer here, like that; and let's go ahead and connect this one, this way, like that.1081

We will put an OH, an OH; this looks like a glucose monomer, so this is CH₂OH.1095

Let's go ahead and make this one a galactose, so we have down.1102

We have up; we have up, and we have CH₂OH.1107

So, this is a globoside- that is it, same thing.1112

You have your ceramide backbone; you have a monomer.1115

You have a monomer; in this case, we have glucose, and we have galactose- that is it, neutral glycolipid.1118

Neutral, glyco - glyco is the sugar part - sphingolipid.1130

Glycolipid, glycosphingolipid, sphingoglycolipid, again, names; structures are what matter.1137

OK, now, let's go ahead and go to our third subclass, which is the gangliosides- very, very important, not that the others are not, but these are, well, anyway, you will see.1148

These have oligosacchs, oligosaccharides as their head group, and 1 or more residues - this is the important part - of Neu5Ac, remember that?1162

N-acetylneuraminic acid, sialic acid - I am just going to go ahead and call it sialic acid - at the terminal positions.1198

In this particular case, at terminal positions; let's see, yes.1212

The gangliosides, what separates them from something else, from the other glycolipids, they have oligosaccharides as their head group, and they have 1 or more residues of the sialic acid at some terminal position.1225

In other words, it ends with some sialic acid residue, 1, 2, 3, however many.1241

Now, recall that sialic acid has - actually, I will write it as recall that Neu5Ac - a negative 1 charge at physiological pH.1249

OK, gangliosides carry negative charge.1287

Now, they are broken down into series; again, just more classifications that make you crazy.1306

I swear, that just drives me insane.1313

So, the GM series, there is 1 sialic acid residue.1316

If you happen to have a ganglioside that has only 1 sialic acid residue, it is part of something called the GM series- that is it.1322

GM1, GM2, GM3, GM4, the M stands for monosialic acid- ganglioside monosialic acid residue.1335

When I have a molecule like GM1, GM2, GM3, that 1, 2, 3, that is part of the name of the molecule- the specific molecule, the specific ganglioside.1343

The M is telling me that that molecule, whatever the particular arrangement of sugar monomers is, that it is going to end somewhere with a 1 sialic acid residue.1356

Personally, I find this very, very confusing; I still find it very confusing.1367

It makes me crazy, but there you go.1371

So, the GM series- 1 sialic acid residue.1374

You have a GD series- disialic acid residue.1380

Here, you have 2 sialic residues, and it goes on like this.1387

You have the GT series; you have the GQ series.1391

Mono, di, tri, quarto, quinto- it just goes on like that.1394

OK, let's go ahead and take a look at a really, really important medical application of a ganglioside biochemistry.1401

Let me go ahead and go on to the next page here for this one.1410

Let's see, yes; let's do this in red.1416

Now, Tay-Sachs disease is caused by the accumulation of ganglioside GM2 in the brain and spleen.1436

OK, these membrane lipids, the body breaks them down and replaces them on a regular basis.1477

It has mechanisms in place; there are specific enzymes that actually break them down, in this particular case, 1 sugar unit at a time, until it ends up with ceramide, and then, the cell takes that ceramide and goes ahead and builds another lipid with it, another ganglioside, say something like that.1485

Well, if there is something wrong with one of these enzymes, and it cannot actually break down, let's say, ganglioside GM3 or GM1 or whatever it is that it cannot break down, it stops.1504

The breakdown process stops, and that particular molecule at that step starts to build up in the cell.1520

The build-up of ganglioside GM2 is what causes Tay-Sachs disease.1527

That is what is happening here, so let's take a look at this.1535

OK.1539

OK, Tay-Sachs disease is caused by the accumulation of ganglioside GM2 in the brain and spleen - actually, let me continue this - because the body lacks the enzyme, in this particular case, this enzyme hexosaminadase A, which catalyzes the following metabolic step.1545

And, since we are talking about a breakdown, we are talking about a catabolic step.1597

Catabolism- it is the breakdown of a molecule into simpler parts.1601

Anabolism is the build-up; it is the biosynthesis.1605

Metabolism is the general term refers to both.1609

So, metabolic, I will just say catabolic step.1612

The body lacks this particular enzyme; it is called hexosaminadase A, and because it lacks it, it cannot break it down past a certain point, and it builds up, builds up, builds up, and then all kinds of terrible things start to happen, and yes, this is, well, yes.1620

OK, here is the particular metabolic step; we have our ceramide.1638

I am just going to write it as our ceramide backbone; I am just not going to write up the whole structure.1642

Let me do this in blue.1646

We have our ceramide, and then we have a glucose residue, and galactose; and then, let's go ahead and do one more here, and let's go ahead and connect one more here.1649

In this particular case, this ganglioside has glucose, galactose, Gal and - it is a little bigger, so I can actually write it in there, so boom, boom, boom, boom, boom, boom - GalNac, N-acetylgalactosamine; and, of course, we have our Neu5Ac, our sialic acid.1670

In this particular case, this is GM2, ganglioside, monoganglioside 2- that is the name, GM2.1696

This particular molecule goes through the particular metabolic step; it is supposed to do this.1704

OK, I have not drawn the oxygens in; I am just using hexagons for the sugars.1712

There is oxygens, of course, on here; but you know that already.1720

So, GalNac, it is supposed to go to ceramide, Glc, Gal; and, of course, we have our Neu5Ac.1725

OK, what is supposed to happen in the metabolic step, the hexosaminadase A - I will go ahead and do this in red - the enzyme catalyzes removing that N-acetylgalactosamine residue off, and takes it to this.1750

This particular molecule is GM3, and, of course, this one goes on in further metabolic steps.1780

We remove this one; we remove the galactose.1786

We remove the glucose, and finally, we end up with ceramide; and the ceramide can go and do what it does.1789

If hexosaminadase is not available, the body lacks this enzyme, this metabolic step cannot take place.1795

If it cannot take place, this molecule ends up accumulating in the brain and spleen; and this is what causes Tay-Sachs disease, so that is what is happening.1803

This is ganglioside, another ganglioside; this is GM2, GM3.1813

There is GM1, GM-whatever; and, again, this M, it stands for 1 sialic acid residue.1818

There is our sialic acid residue; there is our sialic acid residue.1826

This 2 does not refer to the number of sialic acid residues; it just happens to be part of the name- that is it.1830

It is one of those situations where they decided to go with a nice, short name: GM1, GM2, GM3, GM4- that is all that is going on.1838

OK, now, let's go ahead and talk about our last class, which is going to be the sterols.1846

OK, the basic structure of a sterol - why, I really need to start writing a little bit more slowly here - consists of this ring system, where you have these 4 rings that are actually fused together.1856

So, it is going to look something like this; let me see, I will make sure I give myself enough room here.1875

We have that, and we have this, and we have this, and we have that...oops, what am I doing?1880

That is not right; well, it is right, but it is slightly off.1895

It is actually going to be like that, and then, we have this R-group; and I am going to go ahead and put this little OH group because it is either going to be a hydroxy or it is going to be a carbonyl, something like that.1900

This is the basic structure of a sterol, and we call this the A ring, the B ring, the C ring and the D ring, so 6-membered, 6-membered, 6-membered and 5-membered.1911

Now, let me go ahead and just draw out what is probably the most important example of a sterol, certainly the example that you are most familiar with; and this is going to be something called cholesterol or you are more familiar with it as cholesterol- that is it.1922

There is the sterol part; that is the little prefix telling you what it does, what it is.1947

Again, cholesterol, cholesterol- we just shifted the accent a little bit, so it is going to look something like this.1952

Again, the basic structure is going to remain; I am going to have a couple of changes.1959

I am going to have a particular R-group.1963

Let me make sure I have enough room here; there is 1.1967

Let me make this a little bit better; I want to make it as pretty as possible.1973

We are actually going to see an actual picture of it in just a moment, but it is always nice to draw them out, to be able to draw them out by hand, so that is that.1977

Now, let me see here; I have got a double bond here.1989

Let me not forget my hydroxy group; I have got a CH₃ here.1992

I have got a CH₃ here; I have got a C, and a CH₃.1999

And, I have got 1, 2, 3, 4, and 5, so CH₃, CH₃.2007

This is a CH; this is CH₂.2019

This is CH₂; this is CH₂.2022

Let me make sure I have got all my carbons because whenever we start drawing these things by hand, there is always some atom that is missing.2027

1, 2, 3, 4, 5, 6, yes, 1, 2, 3, 4, 5, 6, yes, on this one, we have a CH₃ branching off, CH₃.2032

OK, if I have drawn it correctly, this is our important example of cholesterol.2042

Of course, now, we are going to take a look at some pictures of this.2049

Cholesterol, this is cholesterol; and notice, what we have, this actually shows the stereochemistry.2055

These Hs, this one is out; this one is back.2067

This one is back; this CH₃ group is forward.2070

This CH₃ group is forward; I mean, it is coming out toward us.2073

This is coming out toward us; this is not a problem.2079

This OH group is coming out toward us.2082

Again, it depends on what it is that you are talking about; if you are talking about something where stereochemistry is going to be important, or you are getting into the actual chemistry of the sterol, then yes, you are going to see something like this.2085

If not, then, you will just see regular line structures.2096

OK, I decided to go ahead and bring back this particular illustration down at the bottom half of the page, so you can see, now that we have discussed all of the classes.2100

We have our sphingomyelins here; let's see.2111

We have our sphingosine; we have our C, our C, our C.2116

This is our sphingosine; this is the backbone of the sphingosine right here.2123

And then, we have, of course, the amide linkage, the R-group.2130

And in this particular case, we have the phospho group right there; and it looks like we have got choline right here.2136

So, that is an example of a sphingomyelin.2144

Our cholesterol is this one; that is weird.2148

Why did I put that extra, anyway.2151

This is our cholesterol, and notice, this is outer leaflet; this is inner leaflet, so cholesterol like that.2154

And notice, all of this- nonpolar.2159

These are all just carbon hydrogen bonds; this is just hydrocarbon portion of it.2164

It is the hydrocarbon portion that is actually down inside of it, but this OH is pointing towards the outside.2170

You notice the cholesterol here, the inner leaf, this is inside; and this, the outer - oops, let me go ahead - the OH group is actually pointing in towards the cell.2176

It is actually interacting with the aqueous environment inside the cell; this OH group, the polar part of the molecule, is interacting with the aqueous environment outside the cell.2190

Phosphatidylcholine- this is going to be one of our glycerol phospholipids.2200

Again, you have your long chain, your long chain; you have your phosphate, and on this case, it looks like you have the choline there.2205

OK, now, our inner leaflet, we have the phosphatidylserine; we have another cholesterol, phosphatidylethanolamine, phosphatidylinositol- just something else attached to it.2215

We have our phosphate, our phosphate, our phosphate, so that is it.2228

This pretty much covers the discussion of our membrane lipids.2232

Thank you so much for joining us here at Educator.com2237

We will see you next time, bye-bye.2240