MEH 4 - Lipid Transport Flashcards
How are lipids transported in blood?
What is the total lipid concentration in plasma?
- As they are insoluble in water, they are transported bound to carriers (2% to albumin, 98% as lipoprotein particles)
- 4000-8500 mg/L
Describe the structure of phospholipids
They have a polar head group (choline or inositol), linked to glycerol via phosphate. Attached to glycerol is 2 fatty acid chains (non-polar/hydrophobic tails)
How is cholesterol produced?
What is it an important component of and precursor for?
How is it transported around the body
- Some obtained by diet but mostly synthesised in the liver
- Essential component of membranes (modulates fluidity)
- Precursor of steroid hormones, (e.g.: cortisol) and bile acids
- Transported as a cholesterol ester (cholesterol esterified by LCAT) - has fatty acid group added to end.
Describe the structure of lipoproteins
- Spherical structure w/hydrophobic core, consisting of TAG’s, cholesterol esters and fat soluble vitamins.
- Surrounded by hydrophilic phospholipid monolayer, with small amounts of cholesterol as well as integral and peripheral apolipoproteins.
What are the 5 distinct classes of lipoproteins according to density?
Which ones are the main carriers of fat + cholesterols esters?
Which ones are the densest/contain the highest % protein?
1) Chylomicrons, 2) VLDL , 3) IDL, 4) LDL, 5) HDL
- 1 + 2 main carriers of fat, 3-5 main carriers of cholesterol esters.
- Each contain variable amounts of apolipoproteins, TAG”s, cholesterol (esters).
- Particle diameter inversely proportional to density so VLDL least dense (lowest % protein) and HDL highest density (highest % protein)
What are the 6 major classes of apolipoproteins?
What are their 2 major roles?
- A,B,C,D,E + H (ApoB + ApoAI important)
1) Structural (packaging water insoluble lipids)
2) Functional (co-factor for enzymes + ligands binding to cell surface receptors)
Describe in detail, the process of chylomicron metabolism.
1) Chylomicrons loaded in SI, ApoB-48 added before entering lymphatic system.
2) Travels to thoracic duct which empties into left subclavian vein and acquires ApoC + ApoE once in blood
3) ApoC binds lipoprotein lipase (LPL) on capillary walls of adipocytes + muscle. LPL breaks down chylomicrons into FA’s + glycerol, depleting them of their fat content. FA’s used for energy in muscle, stored as TAG’s in adipose.
4) When TAG reduces to about 20%, apoC dissociates and chylomicron becomes chylomicron remnant.
5) Chylomicron remnant return to liver. LDL receptor on hepatocytes binds ApoE and remnant taken up by receptor mediated endocytosis. Lysosomes release remaining contents for metabolism.
Describe in detail, the process of VLDL metabolism.
1) VLDL’s made in liver for transporting TAG’s to other tissues
2) ApoB100 added during formation, ApoC + ApoE added from HDL particles in blood.
3) VLDL binds to LPL in endothelial cells in muscle and adipose and is depleted of TAG.
4) Muscles uses FA’s for energy production, adipose re-synthesises TAG’s and stores it.
How are IDL’s + LDL’s formed?
1) As TAG’s content of VLDL’s drop, to roughly 30% the particle becomes a short-lived IDL.
2) IDL taken up by liver or rebind to LPL to be further depleted of TAG
3) Depletion to 10% causes loss of ApoC + E, and becomes an LDL particle (with high cholesterol content)
What are the primary functions of LDL’s and their clinical relevance?
LDL’s = provide cholesterol from liver to peripheral tissues. Peripheral cells express LDL receptor for receptor mediated endocytosis of LDL’s. LDL’s have no ApoC or E so not efficiently cleared by liver.
- Half-life of LDL in blood much longer than VLDL or IDL making them susceptible to oxidative damage. Oxidised LDL’s taken up by macrophages and transport into foam cells. Foam cells contribute to atherosclerotic plaque formation.
How do cells requiring cholesterol obtain it?
- Cells will have LDL receptors on plasma membrane
- ApoB-100 on LDL acts as ligand for LDL receptors, LDL taken up by endocytosis into endosomes
- Endosomes fuse with lysosomes for digestion to release cholesterol + fatty acids
- LDL-receptor expression controlled by intracellular cholesterol concentration.
How are HDL’s synthesised + matured?
- HDL synthesised by liver and intestine, but can also “bud off” from chylomicrons and VLDL’s as they are depleted by LDL’s
- Free ApoA-1 can also acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form HDL.
- HDL’s accumulate phospholipids and cholesterol from cells lining blood vessels. Their hollow core fills and particle takes on more globular shape.
What s HDL reverse cholesterol transport?
What ultimately happens to HDL’s?
- HDL’s can remove cholesterol from cells w/alot of it and return it to the liver. This reduces liklehood of foam cell formation and atherosclerosis for blood vessels.
- ABCA1 protein within cell facilitates transfer of cholesterol to HDL, cholesterol then converted to cholesterol ester by LCAT.
- Mature HDL taken up by liver. Cells requiring additional cholesterol can utilise scavenger receptor (SR-B1) to obtain cholesterol from HDL.
Give a summary of the transport function for each lipoprotein covered.
- Chylomicrons = Transport dietary TAG from intestine to tissues, e.g.: adipose.
- VLDL = Transport TAG synthesised in liver to adipose tissue for storage.
- IDL = Short-lived precursor of LDL. Transports cholesterol synthesised in liver to tissues.
- LDL = Transports cholesterol synthesised in liver to tissues
- HDL = Transports excess cholesterol from cells to liver for disposal as bile salts and to cells requiring additional cholesterol (e.g.: for steroid hormone synthesis).
What are hyperlipoproteinaemias + how are they caused?
What are the clinical signs of hypercholestrolaemias?
- Raised plasma levels of 1 or more lipoprotein classes, caused by over-production or under-removal. May be due to defects in enzymes, receptors or apoproteins.
- Due to cholesterol deposition in various areas of the body …
1) Xanthelasma - yellow patches on eyelids
2) Tendon xanthoma - nodules on tendon
3) Corneal arcus - white circle around eye, common in elderly but sign of hypercholestrolaemia in the young.
