Lipid Transport

Question 1

What does saturated fatty acids mean?

Answer 1

There are no double bonds in that structure.

Question 2

Why do we need lipids (fat) in our body?

Answer 2

• Important source of energy and energy store
• Most of our lipids are from our diet
• Vitamins Antioxidants
• Insulation (keeping us warm)
• Protects organs (fat around then to protect from external damage)
• Structural e.g. brain
• Phospholipids (makes up our cell membrane)
• Hormones prostaglandins
• Gene expression
• Essential fatty acids (hormones and cell membrane

Question 3

What are lipoproteins?

Answer 3

They’re formed from lipids and proteins.

• We need them because we need to transport these lipids around our body, so they can get to the various tissues around the body that they need to so they can provide that energy source and provide that cholesterol and lipids to the cell membrane etc.

Question 3

How is fat absorbed in the diet?

Answer 3

• Dietary fat is absorbed as large triglyceride (glycerol +3 fatty acid chains) droplets.
• These droplets get emulsified in our intestine using Bile salts, which then make smaller lipid particles.
• Having smaller lipid particles increase the surface area hence a greater area for enzymes to work on them.
• A key enzyme that works there is pancreatic lipase.
• The pancreatic lipase breaks down the lipids into monoglycerides and free fatty acids.
• The monoglycerides and free fatty acids can now then enter the epithelial cells of the small intestine.
• The bile salts facilitates that transport of monoglycerides and fatty acids into the epithelial cells of the intestines called ‘micelles’.
• In the epithelial cells the monoglycerides and fatty acids combine to form triglycerides again.
• These triglycerides will then aggregate and be coated with lipoprotein (which in this case are called Chylomicrons)
• The Chylomicrons are extruded through the basal membrane of the cells by exocytosis.
• Chylomicrons are unable to cross the basement membrane of capillaries, so instead they enter the lymphatic vessels, the central lacteals.

Question 4

What are the 2 main parts of the lipoprotein structure?

Answer 4

1. Hydrophobic core of lipid, which contains the triglycerides and cholesterol esters.
2. Hydrophilic coat of polar phospholipid, free cholesterol and apoprotein (act as ligands in specific receptors and they help to facilitate the lipoproteins to be taken up into the cells, Apoproteins bind to specific receptors on liver and other tissues)

• This hydrophilic coating is needed so that it can be carried in the blood, as blood is very aqueous and lipids are very fat soluble hence hydrophobic.

Question 5

How do lipoprotein classes differ?

Answer 5

• They differ in relative proportion of core lipids and types of apoproteins (bind to specific receptors)
• There are 5 classes and they differ in size, density and function.

Question 6

What are the 5 different classes of lipoproteins?

Answer 6

1. Chylomicrons (fat absorption from the intestines)
2. Very low density lipoproteins (VLDL)
3. Low density lipoproteins (LDL) (Often known as ‘bad cholesterol’)
4. Intermediate density lipoproteins (IDL)
5. High density lipoproteins (HDL) (Often known as ‘good cholesterol’ because they mostly consist of proteins and main role is to take cholesterol out of the tissue)

Question 7

What are the features of Chylomicrons?

Answer 7

• Largely consists of lipids, mainly triglycerides
• Massive molecules (largest lipoprotein)
• Lowest density -> as they’re mostly made of lipids
• Apoproteins B48 (A,C,E)

Question 8

What are the features of VLDLs?

Answer 8

• Largely consists of lipids, mainly triglycerides
• Smaller than Chylomicron
• More dense than Chylomicrons as they’ve lost some of that lipid
• Apoproteins B100 (A,C,E)

Question 9

What are the features of IDLs?

Answer 9

• Main components are triglycerides and cholesterol, hence were losing some of our lipids (TG) and more cholesterol.
• More denser than Chylomicrons and VLDL but smaller
• Apoproteins B100, E

Question 10

What are the features of LDLs?

Answer 10

• Main component is cholesterol (hence ‘bad cholesterol’)
• More denser than Chylomicrons, VLDL and IDL but smaller
• Apoproteins B100

Question 11

What are the features of HDLs?

Answer 11

• Main component is protein (hence ‘good cholesterol’)
• Most dense lipoprotein (due to large percentage of protein compared to lipids)
• Smallest lipoprotein
• Apoproteins AI, AII (C,E)

Question 12

What is the exogenous lipid pathway?

Answer 12

Where we have lipids coming from our diet.

1. Cholesterol and triglycerides from the diet are absorbed in the ileum, they are then transported in the Chylomicrons to the lymph, blood then capillaries to the muscle and adipose tissue. Chylomicrons basically circulate around the blood and they deliver triglycerides and lipids to the tissues that need them and provide energy.
2. Triglyceride is hydrolysed by an enzyme called lipoprotein lipase. This results in the release of glycerol and free fatty acids release, which are then taken up into tissues and used for energy.
3. Remaining chylomicrons remnants which contain cholesterol esters, travel to the liver and bind to LDL receptors, which are then taken up into the liver cells and are endocytosed.
4. Cholesterol is then stored, and oxidised to bile acids or enters the endogenous pathway.

Question 13

What is the endogenous pathway?

Answer 13

1. Cholesterol (from our diet and newly synthesised in the liver) and newly synthesised triglycerides travel as VLDLs to muscle and adipose tissues.
2. Triglyceride is hydrolysed in the tissue by lipoprotein lipase which breaks it down into glycerol and free fatty acids.
3. Lipoprotein particles become much smaller but still retain cholesterol ester and become LDL. These LDLs then bind to LDL receptors on cells and trigger LDL particles to be taken up into the cell.
4. This then deposits cholesterol into the tissues for cell membranes and other functions.
5. Any left over cholesterol/ cholesterol we don’t need can return to the plasma and liver for tissues via HDL (reverse cholesterol transport), where it can be excreted and taken out of the body.
6. Cholesterol can also become esterified with long chain fatty acid in HDL lipoprotein and transferred to VLDL or LDL in plasma by a protein called cholesterol ester transfer protein (CETP)

Question 14

What does the apolipoprotein ApoB48 do?

Answer 14

In chylomicrons, it is essential for intestinal absorption of dietary lipids.

• So when we got dietary fat coming in, the ApoB48 is really important in taking up those triglycerides and cholesterol into those chylomicrons.

Question 15

What does the apolipoprotein ApoE do?

Answer 15

In chylomicrons, mediates uptake of chylomicron remnants into liver by LDL receptor.

Question 16

What does the apolipoprotein ApoB100 do?

Answer 16

Present in VLDL, IDL and LDL- main physiological ligand for LDL receptor and synthesised/made in the liver

Question 17

What does the apolipoprotein ApoA1 do?

Answer 17

Present in HDL - promotes cholesterol efflux from tissues to liver from excretion.

• Excretes that excess cholesterol, hence having that good cholesterol effect by removing excess cholesterol so that it can’t cause problems in our body.

Question 18

What happens in the LDL receptor pathway?

Answer 18

The LDL receptor is really important for taking up cholesterol and lipids into our liver.

• LDL receptors are found on all nucleated cells but increased expression of LDL receptors on the liver cells - hepatocytes.

1. The LDL lipoprotein itself come in towards the cell. LDL will bind to its receptors on the liver hepatocytes which causes a receptor mediated endocytosis. When this happens the LDL receptor is taken up into these coated vesicles.
2. When it goes into these coated vesicles, theres are drop in pH levels, from pH 7 to pH 5. This drop in Ph levels cause the LDL to dissociate from the LDL receptor. Hence the LDL, lipoprotein and LDL receptor all dissociated.
3. The vesicle then pinches apart into 2 smaller vesicles, 1 vesicle containing the free LDL lipoprotein and the other vesicle with the receptor with no LDL bound to it.
4. The vesicle that has the LDL in fuses with a lysosome, hence a endoscope fusing with a lysosome. The enzymes in the lysosome can cause the release of cholesterol in the lysosome which can be used for membranes, steroid hormones, bole acids, lipoproteins and regulatory actions.
5. We still have a vesicle that contains the empty receptors and we recycle these back onto the cell surface. The recycling vesicle fuses with the cell membrane, turns it inside out, it exocytosis, and the LDL receptors are returned to the cell surface so that they can be used again.

Question 19

What is reverse cholesterol transport?

Answer 19

Net movement of cholesterol from peripheral tissues back to liver.

So when we have excess cholesterol, we can take that away from the cells so it’s not deposited in cells that don’t need it and returns to the liver where it can be excreted.

1. We make HDL in our liver and small intestine and they originate from pre-beta HDL.
2. Pre-beta HDL are very protein rich, disk-like shaped particle. These are empty of any cholesterol.
3. As they start to take up cholesterol from the tissues and are circulating around, the LCAT enzyme esterifies the cholesterol and the HDL molecules become spherical.
4. We can then transfer those cholesterol esters by the enzyme CETP (cholesteryl ester transfer protein).
5. HDL returns back into the liver, and taken back up into the hepatocytes, so the cholesterol that it has been carrying can be excreted.