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Lipoproteins

Q: What kind of lipids are not incorporated in the chylomicron, but go directly into the bloodstream after the enterocytes?

Glycerol, short- and medium-chain fatty acids. Long-chain fatty acids, cholesterol and monoglycerides are packaged into chylomicrons.

32 important questions on Lipoproteins

Why do organs need fatty acids?

- The heart and muscle use fatty acids to burn it in beta-oxidation to get energy (ATP)
- White adipose tissue stores fatty acids in the form of triglycerides
- Brown adipose tissue burns fatty acids, but does not produce ATP, but heat

How are fatty acids transported in the blood?

In lipoproteins, because fatty acids are water-insoluable.

What is cholesterol, what is it needed for, and how is it transported?

- Not a fat, but a sterol (often called a 'fat'),
- and it is needed for

cell membranes
precursor for bile acids
precursor for vitamin D and steroid hormones

- It is also water-insolulable, and therefore transported in lipoproteins.

Why do lipoproteins never contain free fatty acids?

Because free fatty acids are transported through the blood by albumin.

What are 4 types of lipoproteins, and what are the differences?

2 lipoproteins virtually only carry cholesterol acids:

LDL: core is basically just cholesterol acids, quite small. Has apolipoprotein B100
HDL: core has cholesterol acids, has apo A-I and A-II

2 lipoproteins mainly carry triglycerides:

Chylomicrons: has apo B48 (= has 48% of the apo-B transcript)
VLDL

What happens to triglycerides when they are ingested?

(In the intestines) Triglycerides → emulsion droplets → mixed micelles → breakdown → passage of enterocyte membrane

What is the function of lipases (gastric & pancreatic)?

They remove the fatty acids from the glycerol.

By what receptor is cholesterol taken up in the enterocytes?

By the NPC1L1 receptor.

What enzyme produces the precursor of the chylomicron, and how does it do this?

MTP, which lipidates apo-B48 in the enterocyte, which produces the chylomicron precursor.

How is the chylomicron produced, and where is it released?

The apo-B48 is coupled to lipids, and released in the lymphatics, and eventually reaches the blood.

What kind of lipids are not incorporated in the chylomicron, but go directly into the bloodstream after the enterocytes?

Glycerol, short- and medium-chain fatty acids.
Long-chain fatty acids, cholesterol and monoglycerides are packaged into chylomicrons.

What is the function of chylomicrons, and how do they exert this function?

- Function: delivering fatty acids (in the form of triglycerides) to the heart, muscles, white and brown adipose tissue.
- These tissues express LPL,
- with which the chylomicron can interact.
- LPL then turns triglycerides into fatty acids.

What is done with the cholesterol that remains after interaction of the chylomicron with LPL?

That goes towards the liver, and the liver can use the cholesterol for processes.

How are lipoprotein lipases (LPLs) modulated?

By apolipoproteins (e.g. apo-C2 has to be present on the surface of the chylomicron for the LPL to be active).

What apolipoprotein is essential for the chylomicron in order for it to be taken up by the liver?

Apo-E (which it acquires during the 'travel' through the bloodstream)

What allows the uptake of the remnants of chylomicrons by hepatocytes?

The reduction in size, due to the removal of triglycerides from the chylomicrons.
The sinusoids in the liver have fenestrated epithelium, which allows the uptake of the chylomicrons.

What receptors on hepatocytes recognize apo-E?

LDL receptor (LDLr)
LDL receptor related protein (LRP)

How is the pathway called in which lipids and cholesterol are packaged into chylomicrons, the lipids are delivered to the tissue and the cholesterol is taken up by the liver?

The exogenous pathway (because the lipids and cholesterol are from our diet).

How are the chylomicron remnants taken up by the liver?

By endocytosis, after which the triglycerides and cholesterol are separated.

What can the liver do with the triglycerides?

It can package the triglycerides into VLDL (by which MPT (again) is involved to lipidate apo-B100), which is then released in the blood stream.

Why is produced VLDL quite small?

Because it immediately has to pass the fenestrated epithelium of the sinusoids in the liver.
Chylomicrons first become smaller.

Besides apo-B100, what apolipoprotein does the VLDL immediately have?

Apo-E (because apo-E is always produced by the liver, so it is added immediately, unlike the chylomicron, which is produced in the enterocytes).

What does happen to VLDL in the circulation?

VLDL also interacts with LPL, fatty acids are delivered to the organs, and the VLDL remnant can be taken up by the liver because of the recognition of apo-E by LDLr and LRP.
So this is exactly the same as for the chylomicron.

If (almost) all fatty acids are removed from the VLDL, how is the remnant called, and what is done with this remnant?
This specifically happens when the diet was full of fatty acids.

- The lipolytic end product of VLDL is a LDL particle.
- This particle mainly contains cholesterol.
- An LDL particle does not have the apo-E, but only the apo-B100 (so it is not recognized by receptors in the liver!),
- The LDL particle is taken up by peripheral organs (testes, ovaries, adrenals) for the production of androgens, estrogens, membranes, etc.

How is the pathway called in which VLDL is produced by the liver, the fatty acids are delivered, VLDL remnant can be taken up by the liver again, or LDL parcticles are formed?

The endogenous pathway (because the triglycerides and cholesterol did not directly come from the food).

How can LDL cause atherosclerosis, and what can this cause?

damage to the epithelial lining → LDL can start enter the blood vessel wall → inflammatory reaction induced → monocytes/macrophages take up LDL & become foam cells → when the cap breaks, a thrombus can be formed → can cause a stroke or infarction

How could cholesterol leave the vessel wall (in theory)?

By packaging of the cholesterol in HDL (produced by ABCA1 in the liver and small intestine). HDL can take up cholesterol from the vessel wall via receptors ABCA1 and ABCG2.

What are the other things HDL can do (anti-atherogenic)?

- Anti-inflammatory
- Anti-oxidative

If someone has LPL deficiency, what effect can you expect on the plasma lipid (fatty acid & cholesterol) levels?

An increase in plasma triglyceride levels, because the LPL has a role in the removal of those (this does not lead to higher risk on cardiovascular disease).

Mutation in which gene causes a specific increase of LDL in the circulation?

LDLr (because these recognize the apo-B100).
LRP receptor can only recognize apo-E, and LDL does not have apo-E, so a deficiency in LRP would not lead to high LDL levels.

What does mutation in the apo-B48 lead to?

There would be no chylomicron production at all.

How is atherogenic dyslipidemia (high cholesterol) treated?

By statins, which decrease hepatic VLDL production, and also upregulate uptake of LDL by the liver. These two things lower LDL cholesterol (can prevent cardiovascular disease). Important!
Inhibitors of cholesterol absorption (bile salt sequestrants)
Enhance hepatic LDL uptake
Inhibit cholesterol synthesis
Activate brown adipose tissue

Raising HDL (by CETP inhibition) has not worked.

The question on the page originate from the summary of the following study material:

Pathophysiology of Heart & Circulatory System

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