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Flashcards in MEH - Lipid Transport Deck (40)
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Name all the different types of lipids

- triacylglycerol (di- and monoacylglycerol)
- fatty acids
- cholesterol (and cholesterol esters)
- phospholipids
- vitamins A, D, E and K


What is the normal total cholesterol range in plasma?

Less than 5 mmol/L


What is the difference bwteen phosphatidylcholine and phosphatidylinositol?

They are both phospholipids, but phosphatidylcholine has a choline head while phosphatidylinositol has an inositol head


What is the difference between a liposome and a micelle?

Liposomes are spherical but have a bilayer sheet, while micelles have a single layer of phospholipids with their heads facing outwards and tails inwards in a sphere


Where does the body get cholesterol from?

Some is obtained from the diet, but most is synthesised in the liver


What is cholesterol used for in the body?

- essential component of membranes (modulates fluidity)
- precursor of steroid hormones (cortisol, aldosterone, testosterone, oestrogen)
- precursor of bile acids


How is cholesterol transported around the body?

Esterified with a fatty acid by lethicin cholesterol acyltransferase (LCAT) or acyl CoA: cholesterol acyltransferase, then transported around the body as a cholesterol ester


How are lipoproteins structured?

Phospholipid monolayer with a small amount of cholesterol integrated. They also have integral and peripheral apolipoproteins in their membranes (eg. apoC, apoE, apoA, apoB)


What is the cargo carried by lipoproteins?

- triacylglycerols
- cholesterol esters (cholesterol linked to fatty acids)
- fat soluble vitamins


What are the five classes of lipoproteins?

- chylomicrons
- VLDL (very low density lipoproteins)
- IDL (intermediate density lipoproteins)
- LDL (low density lipoproteins)
- HDL (high density lipoproteins)


Which classes of lipoproteins are the largest?

Particle diameter is inversely proportional to density, so chylomicrons are the largest and HDL is the smallest.


When are chylomicrons present in the blood?

Normally only 4-6h after a meal


How is lipoprotein density obtained?

Flotation ultracentrifugation


What are the six major classes of apolipoproteins?

A, B, C, D, E and H

ApoB and apoAI are important ones


True or false - apolipoproteins are all situated on top of the membrane?

False - they can be integral (passing through the phospholipid bilayer) or peripheral (resting on top)


What are the roles of apolipoproteins?

- packaging water insoluble lipid

- co-factor for enzymes
- ligands for cell-surface receptors


How are chylomicrons metabolised?

- chylomicrons loaded in small intestine and apoB-48 added before entering lymphatic system
- travel to thoracic duct which empties into left subclavian vein, acquire two new apoproteins (apoC and apoE) once in blood
- apoC binds to lipoprotein lipase (found on adipocytes and muscle), releasing its fatty acids to cells
- when triglycerides at around 20%, apoC dissociates and 'chylomicron remnant' remains
- this returns to the liver. LDL receptor on hepatocytes binds apoE and the remnant is taken up by receptor mediated endocytosis


What is lipoprotein lipase?

An enzyme that hydrolyses triacylglycerol in lipoproteins. It requires ApoC-II as a cofactor, and is found attached to the surface of endothelial cells in capillaries


What happens to the remaining contents of chylomicrons once they are returned to the liver?

Lysosomes degrade them into fatty acids, cholesterol and glycerol


Where is VLDL made and why?

VLDL is made in the liver for the purpose of transporting triacylglycerol to other tissues.


How is VLDL metabolised?

Binds to lipoprotein lipase on endothelial cells in muscle and adipose and becomes depleted of triacylglycerol. In muscle, released fatty acids are taken up and used for energy production. In adipose, fatty acids are used for re-synthesis of triacylglycerol and stored as fat


How are IDL molecules formed?

If VLDL content depletes to around 30%, the molecule becomes an IDL particle. These can be taken up by the liver or rebind to the LPL enzyme to further deplete TAG content.


How are LDL particles formed?

When IDL content drops to around 10%, it loses apoC and apoE and becomes an LDL particle


What is the primary function of LDL?

To provide cholesterol from the liver to peripheral tissues


Why are LDLs not cleared efficiently by the liver?

They do not have apoC or apoE so they cannot be cleared efficiently by the liver (liver LDL-receptor has a high affinity for apoE)


What is the clinical relevance of LDL not being cleared effectively by the liver?

The half-life in blood is longer than other types of lipoproteins, meaning that it is more susceptible to oxidative damage. Oxidised LDL is taken up by macrophages that can transform to foam cells and contribute to formation of atherosclerotic plaques


How does LDL enter cells?

- cells requiring cholesterol express LDL receptors on plasma membrane
- apoB-100 on LDL acts as a ligand for the receptors, and the receptor-LDL complex is taken into the cell by endocytosis into endosomes.
- fuse with lysosomes for digestion to release cholesterol and fatty acids
- LDL receptor expression controlled by [cholesterol] in cell


How is HDL formed?

- HDL synthesised by liver and intestine
- can also 'bud off' from chylomicrons and VLDL as they are digested by LPL
- free apoA-I can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form nascent-like HDL


How does HDL mature?

- nascent HDL accumulates phospholipids phospholipids and cholesterol from cells lining blood vessels
- hollow core progressively fills and particle becomes more globular

Note - transfer of lipids does not require enzyme activity


What is reverse cholesterol transport?

HDL can remove cholesterol from cholesterol-laden cells and return it to the liver. This is important as it reduces likelihood of foam cell/atherosclerotic plaque formation. ABCA1 protein facilitates transfer of cholesterol to HDL, it is then converted to cholesterol ester by LCAT

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