Lipid Transport Flashcards
What are the 5 types of lipids?
- Triacylglycrerol
- Fatty acids
- Cholesterol
- Phospholipids
- Vitamins (A, D, E and K)
Describe cholesterols
- synthesised in the liver
- essential for regulating membrane fluidity
- precursor of steroid hormones and bile acids
- transported as cholesterol ester
What are lipoproteins?
Biochemical assemblies of lipids and proteins to transport the lipid portion in the blood
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)
each contains variable content of apolipoproteins, TAG, cholesterol and cholesterol esters
What are apolipoproteins?
Proteins that bind to lipids to package them into soluble particles (lipoproteins)
-apoB (VLDL, IDL, LDL) and apoA1 (HDL) are the most important
Describe how chylomicrons come about
1) Dietary lipids absorbed in the intestine (hydrolysed first to fatty acids and glycerol)
2) Re-esterification to triacylglycerols and packaged into chylomicrons
3) apoB-48 added before entering lymphatic system
4) Enters the bloodstream which empties into left subclavian vein and gains 2 new apoproteins (C+E)
5) In the capillary walls of the target tissue (muscle and adipose), lipoprotein lipase hydrolyses them to release fatty acids (apoC binding)
What happens to the remainder of chylomicros (chylomicron remnants)?
1) When chylomicrons release their fatty acids to target tissues (by lipoprotein lipase), apoC dissociates when TAG reduced to ~20%
2) Chylomicron remnant goes to the liver, apoE and chymicron taken up via receptor mediated endocytosis
Where is VLDL made?
Liver
What is the purpose of VLDL?
transporting triacylglycerol to other tissues from the liver
Which apolipoprotein is added during the formation of VLDL
apoB100 (apoC+E added later from HDL)
How does VLDL release its contents to target tissues?
Binds to lipoprotein lipase on endothelial cells in muscle and adipose (same as chylomicrons)
How are IDLs formed?
when VLDL content further depletes to ~30% than returning to the liver
How are LDLs formed?
Further depletion of IDLs to ~10% and apoC and apoE are lost
What is the purpose of LDL?
provide cholesterol from the liver to preipheral tissues (that have LDL receptors in them to be taken up by endocytosis)
What is the clinical relevance of LDLs?
- LDLs have a longer half life (than VLDL or IDL) this makes them more suceptuble to oxidative damage
- oxidised LDLs are phagocytosed by macrophages which ultimately leads to atherosclerotic plaques
Briefly describe the process of Atherosclerosis
1) Oxidised LDL phagocytosed = foam cells
2) Foam cells acumulate in the intima = fatty streaks
3) Fatty streaks evolve to atherosclerotic plaques
4) Growth of plaques lead to angina
5) Further growth leads to ruptured vessels activating acute thrombosis = stroke or myocardial infarction
Where are nascent (empty) HDLs synthesised?
Liver
What is the function of HDLs?
Transport excess cholesterols from cells back to the liver or steroidogenic cells to give cholesterol to form steroid hormones
- can take TAGs from LDLs
- prevent foam cells forming
What is hyperlipoproteinaemia?
Raised plasma level of one or more lipoprotein classes
-overproduction or under removal
What is hypercholesterolaemia?
High level of cholesterol in the blood
What is Xanthelasma?
Yellow patches on the eyelids (cholesterol deposits)
What is tendon Xanthoma?
Nodules on tendons (cholesterol deposits)
What is corneal arcus?
White circle around the iris of the eye (cholesterol deposits)
How is hyperlipoproteinaemia treated?
- Diet
- Lifestyle
- Drugs (statins or bile salt sequestrants)
Describe the mechanism of statins
Inhibits HMG-CoA reductase
-an enzyme in cholesterol synthesis
Describe the mechanism of bile salt sequestrants
They bind bile salts in the GI tract which forces liver to produce more bile acids thus using more cholesterol
