30. Lipid Transport

Question 1

How are lipids transported?

Answer 1

1. The exogenous pathway transports lipid from the gut to the liver
2. The endogenous pathway transports lipids synthesized by the liver to non-hepatic tissue including adipocytes
3. Takes lipids from the circulation and non-hepatic tissue back to the liver.

Question 2

Describe free fatty acids?

Answer 2

1. Formed from triglycerides stored in adipose tissue
2. They circulate and bind to proteins as sodium salt.
3. Fatty acids enter the cells by simple diffusion
4. Intracellular concentration of the free fatty acids is kept low.

Question 3

Describe lipoproteins?

Answer 3

1. Carried in the blood as plasma proteins
2. 5 types of lipoproteins:
3. Chylomicrons
4. Very low density lipoproteins
5. Intermediate density lipoproteins
6. Low density lipoproteins
7. High density lipoproteins

Question 4

Describe Lipoproteins (4pts)

Answer 4

1. Contain a apolipoprotein which has a structural function
2. Contains lipids which form a single layer of lipids with the hydrophilic head groups directed towards the aqueous environment and the hydrophobic fatty acid tails directed towards a hydrophobic core.
3. The hydrophobic core consists of triglycerides and cholesterol esters.
4. On the surface the molecules are phospholipids and cholesterol. They are aligned and associated.

Question 5

Describe Apolipoproteins? (4pts)

Answer 5

1. Structural- help from the particle
2. To solubilise lipids
3. Act as enzymes or enzyme co-factors
4. Tissue targeting

Question 6

Describe dietary lipids? (5pts)

Answer 6

1. Dietary lipids enter the gut as triglycerides.
2. These undergo enzymatic breakdown using lipases to form fatty acids and mono acyl glycerols.
3. These will enter the cell where they reform triglycerides.
4. These triglycerides will form a chylomicron which also contain the protein apo-b-48.
5. The nascent chylomircon will be secreted into the lymphatic system and will drain into the thoracic duct where they will circulate in the body.

• This allows the chylomicron to be distributed to non hepatic tissue before it passes through to the liver.

Question 7

What happens when chylomicron is released into circulation?

Answer 7

1. The nascent chylomicron will interact with HDL where it will pick up apolipoproteins.
2. This forms a mature chylomicron.

Question 8

What happens when chylomicron circulates? (5pts)

Answer 8

1. Lipoprotein lipase is expressed on tissues which metabolise lipids such as muscle, adipose sites and memory glands.
2. The km of LPL isoform in adipocytes is greater than that in the muscle- this means the muscle will take up the fatty acids in preference to the adipose sites.
3. The muscle will till up the fatty acids in preference to the adipose sites.
4. The lipoprotein lipase interacts with the lipoprotein chylomicron which via the APC2 acts as an activator of the lipase.
5. Lipoprotein lipase on adipoctyes is stimulated by insulin with the role of the adipose site which is to store excess lipids.

Question 9

Describe Chylomicrons?

Answer 9

1. Chylomicrons are synthesised in the intestine.
2. They are then released into the lymphatics and then into the circulation where they are acted upon by lipoprotein lipases which are present on the endothelial cell lining of the capillaries that are present in this tissue.
3. The fatty acids are transported into the cell.
4. The remaining chylomicron remnants will be returned to the liver where they will undergo further metabolism.

Question 10

What are the properties of Chylomicrons? (5pts)

Answer 10

1. Reflect meal composition
2. low density due to high triglycerides
3. Contain fat soluble vitamins
4. Half life of the chylomicron in circulation is 1 hour
5. The chylomicron remnants are removed by the liver via binding of Apo E.

Question 11

Describe VLDL?

Answer 11

1. Synthesized by the liver when dietary intake of carbohydrates exceeds immediate needs
2. Triglycerides formed are packaged with free fatty acids, phospholipds and cholesterol esters and Apo B100 to form nascent VLDL.
3. The formation of very low density lipoproteins is stimulated by insulin and inhibited by glucagon.
4. Nascent VDL’s receive ApoE and ApoCII from HDL.
5. Remnants are removed by the liver by ApoE.
6. Half life of triglycerides within the LDL is 15-60 mins

Question 12

Describe the fate of VLDL?

Answer 12

1. LDL arrived from the liver contains ApoE, ApoB100 and Apo CII.
2. The Apo CII will interact and activate the lipoprotein lipase.
3. The triglyceride is then broken down into 3 fatty acids and glycerol which enters the cell. if that cell is an adipose tissue the glycerol and the fatty acid is converted back into a triglyceride and stored. If the cell is a muscle cell the 3 fatty acids are converted into ATP producing CO2 and H20.
4. The LDL’s will continue to circulate in the blood and will form an intermediate density lipoprotein which has a lower triglyceride content.
5. 60% of the LDL’s will be transported back to the liver and will be removed through interaction with its receptor. Some LDL will interact with HDL and will take back the APOe and the APo C2 for future donation to other lipoproteins
6. The resultant liporotein is LDL bound with the APOB1OO Lipoprotein.
7. Some of the LDL’s interact with LDL receptor on non-hepatic tissue and the contents of the LDL will be broken down, removed and used for metabolism.
8. 60-70% of the LDL is returned to the Liver where it is taken up by the LDL receptor.

Question 13

What happens if LDL circulates for too long?

Answer 13

It undergoes oxidation. it is removed from macrophages. If it accumulates too much of this the oxidised LDL can form foam cells which are part of the initiating process of atheroscleoriss regions of the blood vessel.

Question 14

Describe High density lipoproteins ? (6pts)

Answer 14

1. Can be created in 3 ways:
2. As nascent particles by the liver and intestine
3. Budding of apolipoproteins from chylomicrons
4. From free ApoAL.
5. Nascent HDL acquire cholesterol and phospholipids from endothelial cells.
6. Most important function is reverse cholesterol transport.
7. HDL posses LCAT which catalyses cholesterol esterfication preventing it from returning to the cell.
8. Particularly important in vascular cells as it prevents foam cell formation.
9. Cholesterol rich HDL can either deliver it to the liver or exchange it with other particles including VLDL and VLDL remnants.

Question 15

How are lipoproteins removed from circulation? (7pts)

Answer 15

1. The LDL receptor resides on the LDL membrane which will bind LDL
2. The membrane will invaginate a coated pit and will form an endosome
3. The receptor and LDL dissociates within the endosome.
4. The receptor is recycled and expressed back on the cell surface.
5. The LDL will then be broken down following the fusion of the endosome with the lysosomes which contain hydrolytic enzymes.
6. Protein content of the lipoprotein is broken down to the constituent amino acids which is used to build new proteins or further metabolise the triglycerides which will be broken down into glycerol and fatty acids that are used for metabolism.
7. Cholesterol ester that is transported to the LDLS’s are formed back into cholesterol which is incorporated into the er.

Question 16

Describe Familal Hypercholesterolemia (FH)?

Answer 16

1. Single amino acid substitution that prevents the localisation of the LDL receptor to the coated pits so it fails to function adequately.
2. Causes homozygous individuas to have:
3. High serum cholesterol levels
4. Develop blocked arteries due to high cholesterol which leads to atherosclerosis. Foam cells form.
5. Often die young from heart attacks

Question 17

What are the effects of abnormal lipid transport?

Answer 17

1. Diabeties
2. Obesity
3. gene defects