The metabolism and biochemistry of lipids and lipoproteins are the basis for treating cardiovascular diseases like atherosclerosis, ischemic heart disease, and hypertension.

Lipids are hydrophobic molecules that cannot dissolve in plasma, so they need proteins to form lipoproteins that help them travel in the blood.

Today, God willing, we will talk about a very important topic.

And maybe it is the most important thing in the treatment of cardiovascular diseases.

Which is the origin and basis of atherosclerosis, ischemic heart disease, hypertension, and many other diseases.

That we will see in the cardiovascular system.

Which is

metabolism.

And biochemistry.

of lipids and lipoproteins.

Today, God willing, we will talk together.

About

lipids.

And the biochemistry of lipoproteins.

We will talk about their structure.

The pathways in their movement.

Whether the exogenous pathway.

Or the endogenous pathway.

We will talk about HDL.

About these lipoproteinemias.

And about cholesterol.

Let's start together and say.

What's the story?

Why do lipids.

Need help in the first place?

And why isn't it called lipid transport directly?

Lipids by their name.

Are hydrophobic.

They can't move in plasma.

Which is considered.

An aqueous environment.

So they need help from.

Proteins added to them.

To make a completely new thing called.

So the idea is that.

They can't move in plasma.

So they need another help.

And this is the benefit of adding protein to them.

So it becomes called.

Lipoproteins.

And these are what we will talk about today.

With their problems either in excess or deficiency.

And we will understand how they enter the body.

And how they interact with the different body organs.

There are five main classes of lipoproteins: chylomicrons, very low density lipoproteins, intermediate density lipoproteins, low density lipoproteins, and high density lipoproteins.

The lower the density of the lipoprotein, the higher the lipid content and the lower the protein content.

Lipoproteins contain internal content of triglycerides, phospholipids, and cholesterol esters, and on the surface phospholipids, cholesterol, and apoproteins that distinguish each type of lipoprotein.

Apoproteins act as an identification card for each type of lipoprotein and distinguish it from other types.

Chylomicrons carry Apolipoprotein B48 and contain triglycerides and cholesterol esters.

Very low density lipoproteins contain Apolipoprotein B100, E, and C2.

Intermediate density lipoproteins contain Apolipoprotein B100 and E.

Low density lipoproteins contain Apolipoprotein B100 and are rich in cholesterol.

HDL contains Apolipoprotein E, A1, and C2 and transports phospholipids.

Okay, the 5 classes are.

The chylomicrons.

The very low density lipoproteins.

The intermediate density lipoproteins.

The low density lipoproteins.

The high density lipoproteins.

Okay, an important fact.

The lower the density.

Of the lipoprotein.

The higher the percentage.

Of lipids in it.

And the lower the percentage of protein in it.

Okay, let's talk together about lipoproteins.

We said that the body has five lipoproteins.

What do they look like?

They have inside content.

And they have surface content.

We will talk about it.

Here for us, as we see in the picture.

Inside their content there is.

Triglycerides, phospholipids.

And cholesterol ester.

On the surface outside.

There are phospholipids.

There is cholesterol.

And there is something called.

Apolipoproteins.

We can say that apolipoproteins are.

The ID or the personal card.

That the lipoprotein carries.

To be able to distinguish it among.

The other 4 classes.

And each of the 5 classes has.

Its own apolipoprotein.

That can tell me what its name is among them.

Okay, here we have.

This table we need to memorize well.

Because it is of course the topic.

Of questions and MCQs and it.

Really can differentiate.

Between the different types of lipoproteins.

We have chylomicrons.

Their main apolipoprotein.

Is B48 and this distinguishes.

It from the other.

Lipoproteins.

And the core that carries.

Triglycerides.

And cholesterol esters.

The very low-density lipoproteins contain B100 apolipoprotein.

Apolipoprotein E and C2.

C2 is different from E.

Apolipoprotein C2.

And the intermediate-density lipoproteins.

Have apolipoprotein B100.

And apolipoprotein E.

And the low-density lipoprotein.

Its main apolipoprotein is B100.

And HDL has apolipoproteins E, A1, and C2.

Here we are talking about lipids carried in the core.

As we see, the five carry cholesterol ester.

But HDL mainly carries phospholipids.

And the chylomicrons.

The very low density lipoproteins.

And the intermediate density lipoproteins.

Carry triglycerides.

Okay.

Lipids are metabolized in the intestine, liver, and peripheral tissues like muscles, adipose tissue, and adrenal cortex.

In the exogenous pathway, fats from food enter the intestine where chylomicrons are formed that transport fats to tissues via the blood.

Lipoprotein Lipase enzyme on the surface of capillaries in muscle and adipose tissues breaks down triglycerides in chylomicrons to release free fatty acids and glycerol.

Chylomicron remnants enter the liver via LDL and LRP receptors for uptake.

We will talk together about the journey.

Of lipids and say their location.

In the body and where they mainly work.

Lipid metabolism happens in the intestine.

And the liver and extrahepatic tissues.

Like muscles, adipose tissues, and adrenal cortex.

As we will talk about later.

Okay.

Regarding the exogenous pathway, we have lipids entering the body or going to tissues through two organs.

Exogenous pathway.

We eat a fatty meal, something with oils, fried food, red meat.

And so on.

It enters through.

The GIT.

Reaches the intestinal cells.

Inside the intestine, lipids from the diet form chylomicrons.

Chylomicrons are made in the intestine collecting all the fats we ate.

Whether triglycerides, cholesterol.

Whatever type of fat, they form.

And apolipoproteins are added to distinguish them.

Which are Apolipoprotein B48, E, A, and C.

Then they enter the circulation.

So the fats we ate left the intestine and entered the circulation.

They went to the capillaries.

And on the surface of the capillaries, specifically to the tissues that benefit from fats.

Like muscles or adipose tissue.

Lipoprotein lipase enzyme is present.

Lipoprotein lipase, and this lipase is very central in our lecture today because it plays a big role in lipid metabolism.

Lipoprotein lipase simply breaks down and pulls from the chylomicrons to the tissues that the capillaries supply.

We said lipoprotein lipase is on capillaries and these capillaries supply tissues that benefit from fats.

Which are muscles and adipose tissue.

Lipoprotein lipase pulls triglycerides to enter inside the tissues and what remains is the chylomicron remnant.

The chylomicron remnant then goes to the liver.

The chylomicron remnant contains.

ApoB48, ApoE, and cholesterol.

Because triglycerides were left inside the tissues.

Okay, this chylomicron remnant goes to the liver.

And is received and enters the liver via.

LDL receptor and LRP.

We agreed that dietary lipids become chylomicrons in the intestine.

They go to the capillaries, lipoprotein lipase takes triglycerides.

And the chylomicron remnant goes to the liver and is received.

And this is what we said and explained.

Okay, we want to talk about what entered the muscles or.

That continues its work and breaks down into.

Free fatty acids and glycerol. Free fatty acids and glycerol.

These free fatty acids are used in two ways: either during fasting they are broken down in oxidation to produce energy.

Or after eating they undergo esterification.

And are stored again inside tissues for when the body needs them during fasting, for example.

So this is inside.

Let's repeat and increase until we memorize.

And the glycerol or triglycerides go to adipose tissue and muscles.

Glycerol returns to the liver.

And cholesterol and the chylomicron remnant return again to the liver.

Okay, let's talk about the endogenous pathway.

In the endogenous pathway, the liver produces very low density lipoproteins which gradually convert to intermediate density lipoproteins then to low density lipoproteins after losing triglycerides.

LDL is rich in cholesterol and transports cholesterol to peripheral tissues like gonads and adrenal cortex to make steroid hormones.

We have talked about the first source of fats.

Which is.

Exogenous.

Cholesterol.

And triglycerides that we take in the diet.

And how they go.

Let's talk about the body's synthesis.

Of lipids via the liver.

As we see here.

The liver starts with the first stage.

And it is.

Very rich.

Lipoprotein in lipids.

Which is very low density lipoprotein.

And it carries apolipoprotein B100, E, and C.

Low density intermediate density.

Which have apolipoprotein E and B100.

Okay, intermediate density lipoprotein either continues to be broken down and triglycerides are stolen from it by lipoprotein lipase.

It turns into LDL.

Or it stops at this stage and returns to the liver.

To remake very low density lipoprotein from the beginning.

Okay, here we have LDL.

After the IDL has had triglycerides removed.

LDL appears in front of us.

LDL is full of cholesterol.

Here we see LDL.

This LDL is full of cholesterol.

Because all the Triglycerides that were inside

the Very Low Density Lipoproteins

have been taken up in the Extra Hepatic Tissues

like the Adipose Tissue and the Muscles

so the percentage of Triglycerides dropped a lot

so the final compound left for us

which is the Low Density Lipoproteins

became full of cholesterol

Now LDL, if it’s a pathway

it goes to extra hepatic cells like the testis, ovaries, and the suprarenal cortex

to be able to make from the cholesterol it carries

the sex hormones, steroids, and the glucocorticoids

Not all cholesterol is good and not all LDL is good

but everything is within good limits

So how does this LDL enter those extra hepatic tissues via LDL receptors?

And what remains of it returns back to the liver

Here we repeat the explanation again in written form that the liver produces Very Low Density Lipoprotein

which carries these apolipoproteins

Lipoprotein lipase acts on it to take triglycerides from it and convert it to Intermediate Density Lipoprotein

Then when lipoprotein lipase continues to pull from the Intermediate Density Lipoprotein

Low Density Lipoprotein or LDL is formed

whose main apolipoprotein is B100

and part of this LDL goes to extra hepatic tissues

and part of it goes back to the liver

This explains all the things we said and were discussing

between the triglycerides from liver to extra hepatic tissues

Okay

If LDL is not taken up by receptors, cholesterol accumulates in the blood causing severe hypercholesterolemia.

Let’s say that among the most important

lipoproteins are two: HDL and LDL

HDL is called Alpha Lipoprotein

and LDL is called Beta Lipoprotein

And we said it is made

from Very Low Density Lipoprotein

by the action of Lipoprotein Lipase

and it is also made in the liver

and its function is that cholesterol

goes to various tissues

like the testis

and the ovaries and the suprarenal cortex

and it enters those organs

through LDL receptors

But if LDL loaded with cholesterol does not find LDL receptors

What happens? It is loaded with cholesterol and stays in the blood circulation

So severe hypercholesterolemia occurs

Females have a protective mechanism through estrogen

which increases LDL receptors in the liver

So cholesterol does not increase in their blood except in exceptional cases

So now we know the pathway of androgens

which transport the metabolism

and produce LDL loaded with cholesterol that goes to extra hepatic tissues

Now we will talk about LDL receptors

And as we said, if they decrease

severe hypercholesterolemia occurs

and estrogen

protects females

Okay

Now let's come back, we said

and we explained

that triglycerides reaching

tissues like muscles

and adipose tissue

are broken down by lipoprotein lipase

and free fatty acids and glycerol are released

Glycerol goes to the liver

Okay, fatty acids, we said

are used during fasting

in what is called oxidation

to produce energy

But if we are still fed

the body is not in a fasting state

it does not need to burn fatty acids

and use them for energy, so it stores them

in the form of cholesterol and

glycolipids and triglycerides

inside the tissues

If cells receive cholesterol, they stop their own production of cholesterol and on the other hand reduce LDL receptor synthesis. We agreed that LDL is what brings cholesterol to tissues

So when cholesterol enters the tissue and the cell is saturated, down regulation of LDL receptor synthesis occurs

Here we repeat again and say that the journey of the exogenous lipid pathway and the endogenous lipid pathway

We think again here

The diet contained something fatty

in the intestine

chylomicrons were formed

went to the tissues

By lipoprotein lipase

we took all the triglycerides

which were broken down and became

used by the body in oxidation and esterification

and what remains

the remnant went

to the liver, right? Now the liver

from its side as an endogenous pathway

makes Very Low Density Lipoproteins

which go to the capillaries above the tissues

Lipoprotein lipase meets them, breaks them, takes some triglycerides from them

becomes Intermediate Density Lipoproteins

takes some more triglycerides from them

becomes Low Density Lipoproteins

which go to tissues that need cholesterol

like the testis or over the adrenal cortex

to be able to make the 6 hormones and glucocorticoids

and all the remnants go back to the liver

HDL transports excess cholesterol from tissues and other lipoproteins to the liver for breakdown; this is called reverse cholesterol transport.

Now we will talk about HDL and Reverse Transport

What’s the story?

HDL or Alpha Lipoprotein

We have nascent HDL

HDL in its raw form

is exposed to an enzyme in plasma

called lecithin cholesterol acyl transferase

or LCAT

and it converts it to HDL-3

We have Intermediate Density Lipoproteins

Remember them?

They were a transitional stage in the endogenous pathway

Right?

Okay

When an enzyme called

Phospholipid Transfer Protein acts on them

it adds phospholipids to them

and LCAT

or lecithin cholesterol acyl transferase

works on HDL-3

converts it to HDL-2

HDL-2

takes cholesterol

and returns it back to the liver

So this HDL

which takes excess cholesterol

and returns it to the liver

is originally made in the intestine

and in the liver

carries cholesterol from tissues and other lipoproteins to the liver to be catabolized

this is called a reverse cholesterol transport

It is between cholesterol ester and phospholipid

and it is the hormone or enzyme that converts nascent HDL, which is inactive and sitting aside,

to active HDL, which is LCAT

and this happens in plasma

This is an important point because there is

ACAT which is inside the cell

Okay, let’s do a quick review

of the five

Lipoproteins

We have chylomicrons

We said they are classified as from the intestine from the diet

Right

and they transport triglycerides to the peripheral tissues

and when broken down by lipoprotein lipase, glycerol and free fatty acids are produced and the chylomicron remnant is made for the liver

and when the liver makes VLDL from VLDL, it makes lipoprotein lipase and breaks it down to Intermediate Density Lipoprotein then LDL

We said Intermediate Density Lipoproteins are intermediate between Very Low Density Lipoproteins and LDL

They carry triglycerides and cholesterol

and then convert to LDL

which carries cholesterol to tissues

mainly suprarenal cortex and the ovaries and testis

And we said HDL is made in the intestine and liver

It takes cholesterol in what is called reverse cholesterol transport

and takes it back to the liver

and works in plasma with LCAT

Okay