Lipid Transport

Question 1

Give examples of different classes of lipids

Answer 1

• fatty acids
• cholesterol
• TAGS
• phospholipids

Question 2

Why must lipids be carried in the plasma in association with another protein ?

Answer 2

Because lipids are insoluble

Question 3

What are the two examples of ways lipids are carried in plasma ?

Answer 3

1) 98% of lipids are carried by lipoprotein particles
2) 2% of lipids ( mainly fatty acids) are carried in plasma by albumin.

ALL lipids are non-covalently bound

Question 4

Where do we get majority of cholesterol from ?

Answer 4

Most cholesterol is synthesised In the liver

Question 5

Cholesterol is a precursor for….

Answer 5

1) bile salts

2) steroid hormones eg cortisol , aldosterone , testosterone , oestrogen

Question 6

How is cholesterol transported around the body ?

Answer 6

As a cholesterol Ester

Question 7

How is cholesterol converted into a cholesterol Ester ?

Answer 7

It is Esterified with a fatty acid

Question 8

What are lipoproteins ?

Answer 8

They transport water insoluble lipids around the body.

Question 9

Describe the structure of a lipoprotein

Answer 9

• spherical particles
• they consist of a surface coat ( shell ) and a hydrophobic core
• the surface cost contains phospholipid mono layer, small amounts of cholesterol and apoproteins
• the hydrophobic core contains TAGS , cholesterol esters and fat soluble vitamins

Question 10

What are the 5 different classes of lipoproteins ?

Answer 10

1) chylomicrons
2) VLDL ( very low density lipoprotein)
3) IDL ( intermediate density lipoprotein)
4) LDL ( low density lipoprotein )
5) HDL ( high density lipoprotein)

Question 11

What makes the 5 different classes of lipoproteins different ?

Answer 11

They each have variable content of apoproteins , TAGS, cholesterol and cholesterol esters

Question 12

The more dense the lipoprotein ( eg high density lipoprotein ) the …. smaller /larger the diameter and the more/less protein there is

Answer 12

Smaller the diameter

And a high % of protein

Question 13

What are the 6 major classes of apoproteins ?

Answer 13

A B C D E H

Question 14

Where are integral apoproteins found ?

Answer 14

They pass through the phospholipid bilayer of lipoproteins

Question 15

Where are peripheral lipoproteins found ?

Answer 15

They rest on the top of the lipoprotein

Question 16

What are the two roles of apoproteins ?

Answer 16

1) structural role : they package water insoluble lipids into their soluble form.
2) functional roles : act as co factors for enzymes and ligands for cell surface receptors

Question 17

What is the role of chylomicrons ?

Answer 17

• they transport dietary lipids in the small intestine into the lymphatic system. They enter the blood stream at the thoracic duct which empties into the left subclavian vein and are then carried to tissues.
• before entering the Lymphatic system , apoB-48 is added.
• once in blood ApoC and ApoE is added.

Question 18

What is the role of ApoC once it is added to the chylomicrons when it entered the blood circulation a.

Answer 18

ApoC Binds to lipoprotein lipase on adipocytes and muscle.

• the enzyme hydrolyses the TAGS that were carried by the chylomicrons , releasing fatty acids. Which are either recombined back into TAGS in adipose tissue for storage or are used to generate energy in muscles.
• when there has been a 20% depletion in TAGS, ApoC dissociates and chylomicrons becomes a chylomicrons remnant which is then taken up by the liver.

Question 19

Where is VLDL made ?

Answer 19

In the liver

Question 20

What is the function of VLDL?

Answer 20

Transport of TAGS synthesised in the liver to adipose tissue for storage

Question 21

Explain how VLDL transports the TAGS from the liver ?

Answer 21

• apoproteins ApoB100 is added during formation of VLDL.
• ApoC and ApoE is added from HDL particles in the blood.
• VLDL binds to lipoprotein lipase on endothelial cells in muscle and adipose and begins to become depleted of TAGS.

-

Question 22

What is the function of IDL?

Answer 22

Short lived precursor for LDL.

Question 23

What happens to VLDL as the TAGS content depleted by 30%?

Answer 23

• the particle becomes a short lived IDL particle.
• IDL particles can also be taken up by the liver or rebind to LPL enzyme to further deplete TAG content.
• upon depletion of TAG content of IDL by 10% , IDL loses ApoC and ApoE to become an LDL particle.

Question 24

What is the function of LDL?

Answer 24

TRANSFER OF CHOLESTEROL FROM THE LIVER TO PERIPHERAL RECEPTORS

• these peripheral tissues express LDL receptors and take up LDL via receptor mediated endocytosis

Question 25

What is one difference between IDL and LDL ?

Answer 25

LDL does not have ApoE or ApoC so are not efficiently Cleared by the liver.

Question 26

Which has a higher cholesterol content - LDL or HDL ?

Answer 26

LDL

Question 27

How can LDL lead to the formation of atherosclerotic plaques ?

Answer 27

- half life of LDL is much longer than IDL and VLDL making LDL more susceptible to oxidative damage - once oxidised , it is taken up by macrophages that cam transform to foam cells and contribute to the formation of these plaques.

Question 28

Cells that require cholesterol would require what type of receptors ?

Answer 28

LDL receptors

Question 29

How does LDL enter cells by receptor mediated endocytosis ?

Answer 29

1) ApoB-100 on LDL acts as a ligand for these LDL receptors one plasma membrane. 2) receptor - LDL complex taken into cell by endocytosis into endosomes 3) endosomes fuse with lysosomes for digestion to release cholesterol and fatty acids.

Question 30

What is the function of HDL?

Answer 30

TRANSPORT OF EXCESS CHOLESTEROL FROM THE TISSUES TO THE LIVER FOR DISPOSAL AS BILE SALTS AND TO CELLS REQUIRING CHOLESTEROL

Question 31

How is HDL synthesised ?

Answer 31

Nascent HDL is synthesised by the liver and intestine - HDL particles can also bud off from chylomicrons and VLDL as they are digested by lipoprotein lipase -

Question 32

How does HDL reverse cholesterol transport ?

Answer 32

HDL have the ability to remove cholesterol from cholesterol laden cells and return it to liver - this is important for blood vessels as it reduces the likelihood of foam cells and atherosclerotic plaque - ABCA1 protein within cell facilitates transfer of cholesterol to HDL. Cholesterol then converted to cholesterol Ester by LCAT.

Question 33

Cells requiring additional cholesterol can utilise what receptor to obtain cholesterol from HDL?

Answer 33

Scavenger receptor

Question 34

What protein is used when HDL wants to exchange cholesterol Ester with TAG from VLDL?

Answer 34

Cholesterol exchange transfer protein

Question 35

Define hyperlipoproteinaemias

Answer 35

After a period of fasting , (12 hours) Raised plasma level by one or more lipoprotein classes - caused by over production or under removal

Question 36

What are 3 clinical signs of hypercholesterolaemia?

Answer 36

1) Xanthelasma : yellow patches on eyelids 2) tendon Xanthoma : nodules on tendons 3) corneal arcus : obvious white circle around eye. Common in elder people , but if in young it is a clinical sign.

Question 37

How is raised LDL associated with atherosclerosis?

Answer 37

1) raised LDL increases likelihood of oxidative damage. 2) LDL becomes oxidised. 3) recognised and engulfed by macrophages 4) lipid laden macrophages called foam cells accumulate in intima of blood vessel walls to forms. Fatty streak 5) fatty streak evolves into atherosclerotic plaque 6) grows in lumen of artery = angina 7) artery ruptures= this triggers acute thrombosis leading to stroke or MI

Question 38

How to treat someone with hyperlipoproteinaemia ?

Answer 38

FIRST APPROACH : 1) reduce cholesterol and saturated lipids in diet, increase fibre intake 2) increase exercise , stop smoking SECOND APPROACH : 1) statins which inhibits HMG coA. Reducing cholesterol synthesis 2) bile salt sequestrants: bind bile salts in GI tract , which forces lover to produce more bile so uses more cholesterol.

Question 39

What is the ideal total cholesterol concentration ?

Answer 39

5mmol/L or less

Question 40

What is the ideal LDL cholesterol conc ?

Answer 40

3mmol/less

Question 41

Ideal HDL- cholesterol level ?

Answer 41

Ideally over 1mmol/L

Question 42

Ideal total cholesterol :HDL-C ratio ?

Answer 42

Ratio above 6 considered high risk. The lower the ratio the better.