4 - Lipid Transport Flashcards
How are lipids carried in the blood if they are insoluble in water?
- Lipoproteins
- Albumin (limited capacity so only carries 2%)
Why is the normal level of total cholesterol in the blood?
< 5mmol/L
How are phospholipids classified?
According to their phosphate head, e.g phosphatidylinositol (signalligng molecule)
Where is cholesterol synthesised, what is it the precursor of, and what form is it transported in the blood?
- Some diet but mainly liver
- Precursor of steroid hormones, membranes and bile salts
- Carried as cholesterol ester
What is the structure of a lipoprotein?
What are the five classes of lipoproteins and what do they carry?
Chylomicron remnants - Removal of lipids from chylomicrons
Different lipoproteins due to different apolipoproteins
What lipoproteins are the main carriers of fat and what ones mainly carries cholesterol esters?
Fat: Chylomicrons, VLDL
C Esters: IDL, LDL, HDL
What would be the main differences in HDL and VLDL?
- More dense = more protein
- More dense = smaller diameter
What would blood plasma look like 4-6h after a meal and why?
Creamy appearance due to the presence of chlyomicrons that feed into the left subclavian vein from the thoracic duct
What are the role of apolipoproteins?
- Six classes (A,B,C,D,E and H)
Structural: Package water insoluble lipid
Functional: Co-factor for enzymes, ligand for cell surface receptors
How are chylomicrons metabolised?
- Chylomicrons loaded in SI and apoB-48 added before entering lymph
- Acquires apoC and apoE in blood
- ApoC binds lipoprotein lipase on inner surface of capillaries around adipocytes and muscles.
- Releases FA into cells, depleting chylomicron of fat
- When TAG <20%, apoC dissociates and it is a chylomicron remnant
- Remnant returns to liver, LDL receptor on hepatocytes bind to apoE and remant taken up by receptor mediated endocytosis
- Lysosomes release remaining contents to use for metabolism
How are VLDL metabolised?
- Made in liver to transport TAG
- ApoB100 added during formation and acquires apoC and apoE from HDL in blood
- VLDL binds to LPL
- In muscle FA are used for energy, in adipose stored as fat
- Content depletes <30%, becomes IDL. VLDL may dissociate before this happens and return to liver
What happens to a IPL?
Can either be taken up by liver, OR rebind to LDL and deplete TAG content.
Deplete <10% IDL will lose apoC and apoE and become LDL, with high cholesterol content
What is the function of LDL and how is it metabolised?
- Provides cholesterol to cells
- Cells that require cholesterol express LDL receptors and apoB-100 acts as ligand for these.
- Receptor mediated endocytosis
- Lysosomes fuse and digest to release cholesterol and FA
What is the issue with LDL?
- Not efficiently cleared by liver as no apoE (and apoC) on surface
- Much longer half life in plasma so susceptible to oxidative damage and lipid peroxidation
- Oxidised LDL taken up by macrophages, forming foam cells causing fatty streak and atherosclerosis
How are HDL particles synthesised and matured?
Synthesis:
- Empty low TAG in SI and liver
- Can bud off from chylomicrons and VLDL as they are digested by LDL
- ApoA-I can aquire cholesterol and phospholipid from cell membranes and lipoproteins to form HDL
Maturation:
- Reverse cholesterol transport (non-enzymatic) from cells lining blood vessels
- ABCA1 protein transporter facilitates transfer of cholesterol to HDL which is then converted to ester by LCAT
What happens to HDL after it has matured?
- Can return to liver and be turned into bile salts
- Cells requiring cholesterol use scavenger receptor, SRB1 to get cholesterol for steroid synthesis
- Exchange cholesterol for TAG with VLDL with cholesterol exchange transfer protein (CETP)
What is the signs of dyslipoproteinaemias?
Defects in the metabolisms of lipoproteins, which can be primary or secondary.
What are the different classes of hyperlipoproteinaemias?
- Raised plasma level of one or more lipoproteins due to underremoval or underproduction
- Classified by fastin plasma concetrations of glucose, total cholesterol and TAG, electrophoresis of lipoproteins
How do you treat hyperlipoproteinanaemia?
Statins have a lot of side effects as stop a lot of intermediates, need to be careful with this
What are the signs of hypercholesterolaemia?
Corneal arcus normal in old people but in young people it is a sign of the condition
When looking at cholesterol levels on blood test, when is someone high risk for cardiovascular disease?
Total cholesterol:HDL ratio is above 6
How can hypercholesterolaemia be a genetic disease?
- Could have a genetic defect in the lipoprotein lipase gene so cannot break down chylomicrons
- Could be making too much cholesterol
What are the problems of a low fat diet?
- Not enough energy
- Cannot absorb fat soluble vitamins
- Some ‘essential’ fats
What is gluconeogenesis?
When are the different energy stores in the body used?
What products can be synthesised by acetyl coA directly?
Explain why individuals with a defect in the enzyme lecithin- cholesterol acyltransferase produce unstable lipoproteins of abnormal structure. What are the clinical consequences of this defect?
