Biochemistry Fatty Acid Catabolism I

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

We just finished discussing the citric acid cycle and the breakdown of carbohydrates.0004

Now, we are going to start discussing the breakdown of the fats, of the lipids.0010

We are going to be discussing fatty acid catabolism, so let's just jump right on in.0016

OK, the oxidation of fatty acids to acetyl-CoA, you notice that fatty acids are also catabolized to acetyl-CoA just like the pyruvate was that entered the citric acid cycle.0022

It is broken down into acetyl-CoA, and these acetyl-CoAs actually enter the citric acid cycle.0050

The oxidation of fatty acids to acetyl-CoA is a major source of energy for organisms.0055

In fact, it is probably the major source.0070

OK, complete oxidation of fatty acids - I will just go ahead and abbreviate it as FAs - releases about 40kJ/g.0075

For a gram of fat, it releases about 40kJ of heat - that is a lot of energy - more than twice that released by an equal mass of either protein or carbohydrate.0101

OK, now, vertebrate cells obtain the fatty acids that they need - obtain FAs - for catabolism from 3 sources.0137

In other words, the fatty acids that the cell needs in order to burn to get energy, they come from 3 different sources.0168

There are 3 ways that the fatty acids get to the cells, in other words.0176

One of them is diet.0180

What you eat, it finds its way directly to the cells.0184

Two: is the fats that are stored in cells already.0189

Sometimes, it will just mobilize those fats that are already there and use them for breakdown, and the third way is the fats that are synthesized by one organ then, transported to the tissues that need them.0199

OK, let's talk about diet first.0237

No. 1: diet, dietary fats are absorbed by the small intestine.0242

Now, we will just go ahead and list how it actually does this.0268

In your biochemistry books, there is probably some illustration of some sort that talks about how it goes from the intestine, how it gets here.0272

You are more than welcome to look at it; in fact, I encourage you to take a look at it.0279

What I am going to do here, I am not really going to be using any diagrams.0283

I am just going to be listing the process; it is important to know what happens, but we want to concentrate on the second one, the fats that are stored in cells, how those fats are actually mobilized, and that is when we are going to be looking at diagrams and pictures and following reactions very carefully.0286

Dietary fats are absorbed by the small intestines, and it happens as follows.0301

Bile salts emulsify dietary triacylglycerols.0309

Triacylglycerol, just fat, the fat that you ingest, you are ingesting it as triacylglycerols.0325

The bile salts that the body secretes actually emulsify them.0332

OK, now, 2: lipase enzymes, they break down these triacylglycerols - which I will abbreviate as TAGs - to monoacylglycerols, diacylglycerols, free fatty acids - free fatty acid, those are just those long chain carboxylic acids, we just call them free fatty acids - and glycerol.0336

OK, now, no. 3: these breakdown products, they are what is actually absorbed by the intestine.0380

These breakdown products are absorbed by the intestine.0395

OK, now, no. 4: these breakdown products - well, I will write that again - are reconverted back to the triacylglycerols, then, these TAGs are combined with cholesterol, cholesteryl esters and - excuse me - specific proteins into particles called chylomicrons; and certainly, there is a picture of a chylomicron in your book.0408

These triacylglycerols that are reformed, they are combined with cholesterol and the esters of cholesterol.0492

Cholesteryl ester is actually an ester of cholesterol, and these specific proteins, they are, sort of, combined into this particle.0502

The proteins are on, sort of, the outside of it, and these particles are called chylomicrons.0510

OK, I want to say a word about these specific proteins.0517

Now, these specific proteins are called apolipoproteins, and they are responsible for actually transporting the lipids through the bloodstream because fats, as you know, are not water soluble.0521

So, they cannot just float around in the blood or the lymph.0551

They have to be solubilized - if you will - by these proteins.0557

They attach to proteins, and the proteins carry them to where they need to be.0561

These specific proteins are called apolipoproteins, and they are responsible for transporting insoluble lipids through the bloodstream and lymphatic system.0565

OK, one of these proteins, APOC2 is an example.0604

That is the name of it- APOC2.0613

OK, excuse me; let's see what happens next.0617

Alright, no. 5: these chylomicrons are transported via blood and lymph to the various tissues.0623

OK, now, no. 6: in the capillaries, when they reach the end of their respective journeys, the enzyme lipoprotein lipase - or lipase if you want, I say lipase - recognizes the APOC2 that I mentioned earlier - one of those lipoproteins, it recognizes the APOC2 - and starts breaking down, hydrolyzing - yes, that is fine - the triacylglycerols, the TAGs to free fatty acids and glycerol- that is it.0653

And then, the fatty acids, at this point, that is when they enter the cells.0725

Fatty acids enter cells of the tissues, at this point.0732

OK, now, no. 8: OK, the fatty acids, once they are in the cell, the FAs are either oxidized to release the energy, or they are re-esterified to store as triacylglycerols.0745

They are reesterified - in other words, the free fatty acids and the glycerol are put back together in order to store them for future use - to the triacylglycerols, which they were originally, for storage, and that is it.0786

OK, now, let's go ahead and talk about...this is how the fats that we ingest in our diet, how they get to the particular cells.0807

Now, the other way that free fatty acids, that triacylglycerols, the fats, are actually mobilized in order to be used are there are the fat that is actually stored in the cells, how do we use that fat?0818

Well, now, we will talk about that.0832

No, 2: let's go ahead and do this one in blue.0836

No. 2: fats that are already stored in adipocytes - adipocytes, however you want to pronounce it - fat cells.0840

They are cells where fat is stored as just as fat, just straight triacylglycerols.0854

OK, now, excuse me.0863

Fats stored in adipocytes are mobilized by the hormones glucagon and epinephrine, which are secreted by the body in response to low blood glucose levels.0868

If your blood glucose rises too high, at that point, that is when the body pumps in insulin.0925

That is the hormone that starts to break that down to regulate high blood glucose.0929

If your blood sugar drops too low, glucagon and epinephrine are secreted, in order to, in this particular case, mobilize free fatty acids.0935

That is all that is going on here; OK, now, let's run through the process.0944

Now, in this particular case, what I am going to do is I am going to list the process 1, 2, 3, 4, 5, and then, we will actually take a look at a diagram of a cell, so that we can see it visually as well.0948

I would like you to have it written out, and I would like you to also have it visually, so we will go through this twice.0958

If there is anything in the written part that you do not necessarily understand, we will go through it again, and we will see it.0965

When we see it pictorially, it should make sense what is happening in the cell.0969

OK, no. 1: now, the hormone, it stimulates the enzyme - well, you do not have to - it stimulates adenylyl cyclase via a G protein to produce cyclic adenosine monophosphate.0974

There is this enzyme that is in the outer membrane, and it stimulates this adenylyl cyclase via something called a G protein to produce this thing called cyclic adenosine monophosphate.1023

OK, now, 2: cyclic adenosine monophosphate - cAMP - it is a secondary messenger inside the cell, which induces a protein called cAMP-dependent protein kinase to phosphorylate 2 things, right?1037

A kinase does 1 thing, so this cyclic adenosine monophosphate is a secondary messenger.1085

It stimulates this cAMP-dependent protein kinase to phosphorylate 2 things.1090

OK, the first thing that it phosphorylates is something called a hormone-sensitive lipase, and we know what lipases do.1108

Lipases break down lipids, triacylglycerols.1118

OK, it also phosphorylates something called a perilipin.1122

It also phosphorylates something called the perilipins, which are proteins on the outer surface of the lipid droplets that is in the cell.1128

The fat that is in the cell that is, sort of, aggregated on the surface of that fat collection are these things called perilipins on the outer surface of the lipid droplets in the adipocytes.1157

OK, no. 3: OK, hormone-sensitive lipase, once it phosphorylates this thing called hormone-sensitive lipase, the hormone-sensitive lipase, which is floating around in the cytosol, it actually moves around in the droplet, moves toward the lipid droplet, and it starts hyrdolyzing the triacylglycerols.1182

It starts breaking them down - the triacylglycerols - into free fatty acids and glycerol.1230

It basically takes those triacylglycerols and just cuts them off to release the free fatty acids and to release the glycerol.1245

OK, now, let's go to no. 4.1253

Now, the free fatty acids, they pass from the adipocyte into the blood stream.1259

The free fatty acids pass from the fat cell - from the adipocyte - to the bloodstream where they combine with, where they bind to a protein called serum albumin - bind to serum albumin protein - which then, carries them to the various tissues - cells - where they are needed.1270

We have these cells, adipocytes, it is where the fat is stored.1337

If that fat is needed for some purpose, let's say you have not eaten all day, but the body needs some energy, and it wants to actually burn some fat, it is going to burn some of the fat that you have stored.1342

It is going to mobilize this fat, and once it breaks it down into the free fatty acids, it sends those free fatty acids outside of the fat cell into the blood stream, so that the blood stream, the serum albumin, can take those bound-free fatty acids to the cells, to the muscle tissue, in order to mobilize it and extract the energy.1355

That is all that is happening there; now, that takes care of the free fatty acids.1375

What about the glycerol?1379

OK, the glycerol left behind, and then, we have to account for everything.1380

We are not just going to leave molecules just hanging around and say nothing about them.1389

The glycerol that is left behind is phosphorylated by - you guessed it - glycerol kinase because that is what kinases do - they phosphorylate - to glycerol 3-phosphate, not glyceraldehyde-3-phosphate- glycerol 3-phosphate.1393

It is this; glycerol goes to glycerol 3-phosphate, which is then, converted into dihydroxyacetone phosphate, which is then, converted to glyceraldehyde-3-phoaphate; and you can see where we are going.1428

Glyceraldehyde-3-phosphate continues on with glycolysis.1452

It has ways of handling what is left over, and that is all that happens.1459

OK, now, what we want to do, now, that we have actually written this out, let's go ahead and take a look at a picture of this, and see what it looks like; so let's see here.1463

I think I have got it here; yes, here we go.1473

OK, do not worry; there is a lot going on here, but it just seems that way.1477

Once we actually start talking about what is going on, you are going to realize that everything is really, really, very, very clear.1482

Let's identify some things here; this is the fat cell.1488

OK, and this thing right here, this is the lipid droplet.1493

It is just a collection, an aggregate of fat- triglycerols.1498

This is the cell; now, on the cell surface, there is a receptor for the particular hormone.1504

In this particular case, whether it is glucagon or epinephrine, it does not really matter.1507

The hormone attaches to the receptor; it has been secreted by the body.1512

It attaches to the receptor; this receptor, now, via something called the G protein - do not worry about it if you do not know what the G protein is.1516