Lipid Transport Flashcards
Why do lipids need to be transported via lipoprotein particles?
Lipids are not water-soluble, and so need to be transported in a hydrophilic particle through the blood.
Name the classes of lipids.
Phospholipids Triacylglycerol Fatty acids Cholesterol Cholesterol esters
How can lipids be transported?
2% = FA-albumin (limited capacity)
98% = carried as lipoprotein particles (synthesised in liver)
How can lipoproteins vary?
Size Apolipoprotein composition Density Surface charge Function
What are the different lipoprotein particles arranged by increasing density? What substances do they transport and where?
CHYLOMICRON = Lipids absorbed from small intestine -> Liver, skeletal muscle, adipose, cardiac muscle
VERY LOW DENSITY LIPOPROTEIN = Lipids (liver) -> Adipose Tissue
LOW DENSITY LIPOPROTEIN = Cholesterol (liver) -> Tissues
HIGH DENSITY LIPOPROTEIN = Cholesterol (tissues) -> Liver
Describe chylomicron-assisted transport.
Enterocytes lining small intestine absorb and reassemble TAGs using specific apoproteins (cholesterol present in the shell). TAGs transported to tissues.
Unloading catalysed by lipases on endothelial cells of capillaries.
Normally present in blood only 4-6hrs after a fatty meal (thick brown urine)
Transported via lymphatic system into the blood, bypassing liver.
Lacteal -> Lymphatic system -> Thoracic duct -> Subclavian vein
Describe VLDL-assisted transport.
TAGs in liver transported to adipose tissue via the blood.
Unloading catalysed by lipases on the endothelial cells of capillaries.
Remnants of VDLs removed by liver or converted to other lipoprotein particles
Describe LDL-assisted transport.
Cholesterol synthesised and combined with specific apoproteins in the liver and transported to tissues via the blood.
Unloading when LDL receptors on cell surface recognise Apo B-100. Receptor-LDL complex endocytosed. Cholesterol ester cleaved to release cholesterol and fatty acids.
LDL receptor expression regulated by [cholesterol]
Describe HDL-assisted transport.
Excess cholesterol in the tissues is transported back to the liver and small intestine via the blood.
Loading: nascent HDL shells synthesised in liver. Sequesters cholesterol from capillaries and becomes mature HDL particles.
Excess cholesterol in liver converted to bile salts.
Describe atherosclerosis and why it is associated with a high LDL. Why can atherosclerosis cause MI/strokes?
Oxidised LDLs deposit in the intima of artery walls -> engulfed by macrophages -> foam cells -> accumulation & swelling -> fatty streak –> atheroma
LDLs deposit cholesterol in tissues.
Narrowed lumen or plaque rupture + thrombus -> occlusion of artery -> MI (cardiac artery) or stroke
What are hyperlipoproteinaemias?
Raised levels of one or more lipoprotein classes in the blood.
Due to over-production or under-removal.
Can be due to defective enzymes, defective receptors, or polymorphisms of apoproteins.
What are the signs and symptoms of hypercholesterolaemia?
Xanthelasma = lipid deposits under skin in eyelids
Tendon xanthoma = lipid accumulates in tendons
Corenal arcus = deposit of lipids around cornea
How is hypercholesterolaemia treated?
Diet & lifestyle = reduce cholesterol and saturated lipid content (however, some cholesterol will still be synthesised in the liver from acetyl-CoA)
+ stop smoking/reduce drinking to reduce risk of atherosclerosis and associated CVD
Statins e.g. simvastatin = inhibits HMG-CoA reductase to reduce cholesterol synthesis, increases expression of LDL receptors in hepatocytes, and anti-inflammatory?
note: lots of side-effects + may need to take coenzyme Q10 supplements
