Lipid Transport Flashcards
Why is it difficult for lipids to be transported in the blood?
They are hydrophobic
So I soluble in water
How are lipids transported in the blood? (2)
Bound to albumin
As lipoprotein particles
What are the four components of phospholipids?
Polar hydrophobic head
Phosphate
Glycerol
Non polar fatty acid tail
How are phospholipids classified?
Give two examples
According to their polar head
Choline
Inositol
Where are the two sources of cholesterol?
Obtained from diet
Synthesised in the liver
What are three uses of cholesterol?
Modulates fluidity of membrane
Precursors of steroid hormones
Precursors of bile acids
How is cholesterol transported?
As cholesterol esters - linked to a fatty acid
What are the two types of proteins in a lipoprotein?
Peripheral apolipoproteins - on the outside
Integral apolipoproteins - pass through
What is the cargo of a lipoprotein made up of?
Triacylglycerol
Cholesterol ester
Fat soluble vitamins (ADEK)
What are the five classes of lipoproteins?
Chylomicrons
VLDL
IDL
LDL
HDL
How are lipoproteins classed?
How is this measurement obtained?
According to their density
Flotation ultracentrifugation
Compare the diameter of lipoproteins with their density
Describe an example
Inversely proportional
VLDL - lowest density but highest diameter
How many classes of apolipoproteins are there?
Name the two important ones
Six
ApoB apoAI
What are the two roles of apolipoproteins
Structural - package water insoluble lipid
Functional - ligands for cell surface receptors and cofactors for enzymes
Describe Chylomicron metabolism
- Produced in the small intestines
- ApoB48 added
- Enters lymphatic system
- Travels though thoracic duct into the left subclavian vein
- Acquires apoC and apoE
- ApoC binds to lipoprotein lipase on adipocytes and muscle
- Fatty acids are released from chylomicron into the cells
- When triglyceride levels are depleted to 20% apoC dissociates - leaving a chylomicron remnant
Describe what happens to the chylomicron remnants
- Return to the liver
- LDL receptors of hepatocytes bind to the apoE (on them)
- The remnant is taken up by receptor mediated endocytosis
Where are VLDL made?
What is their purpose?
Liver
Transport triacylglycerol
Describe VLDL metabolism
- ApoB added during formation
- ApoC and apoE added from HDL particles in blood
- VLDL bind to lipoprotein lipase on endothelial cells - in muscle and adipose
- VLDL starts to be depleted of triacylglycerol
What happens to the triacylglycerol in adipose and muscle cells during VLDL metabolism?
Muscle - fatty acids taken up and used for energy production
Adipose - used for resynthesis of triacylglycerol and stored as fat
What is derived from VLDL?
IDL and LDL
Describe the formation of IDL
- Triacylglycerol content of VLDL particle drops
- Some VLDL particles dissociate from the lipoprotein lipase enzyme complex and return to liver
- If it depletes to 30% it becomes an IDL
Describe the formation of LDL
- IDL particle rebinds to LPL enzyme
- Further depletion in triacylglycerol content
- Depletion to 10% - IDL loses apoC and apoE
What is the primary function of LDL?
How does this happen?
Provide cholesterol from liver to peripheral tissues
Peripheral cells have LDL receptors
Take up LDL via receptor mediated endocytosis
Why are LDL more susceptible to oxidative damage?
Do not have apoC or apoE - not efficiently cleared by liver
Half life in blood is longer
What happens to oxidised LDL?
Taken up by macrophages
Transform to foam cells
Contribute to formation of atherosclerotic plaques
Where is lipoprotein lipase?
On endothelial cells
In muscle and adipose
What is the process in which LDL are taken into peripheral cells?
Receptor mediated endocytosis
Describe receptor mediated endocytosis of LDL
- ApoB100 on LDL acts as a ligand
- Binds to LDL receptors on plasma membrane of peripheral cells
- LDL complex taken up by endocytosis - into endosomes
What happens to LDL once inside of peripheral cells?
Fuse with lysosomes for digestion
Fatty acids and cholesterol released
What is LDL reactor expression controlled by?
Cholesterol conc in cell
Where is HDL synthesised (2)
Liver
Intestine
How are HDL particles also made? (2)
Bud off from chylomicrons and VLDL as they are digested by lipoprotein lipase
Free apoA can acquire cholesterol and phospholipids from other lipoproteins and cell membranes
How do HDL become mature and globular?
HDL accumulate phospholipids and cholesterol from cells lining blood vessels
Describe HDL metabolism
- HDL remove cholesterol from cells containing cholesterol - facilitated by ABCA1 protein
- Cholesterol converted to cholesterol ester by LCAT
- Return cholesterol to liver
Why is the fact HDL can remove cholesterol from cells important?
Reduces likelihood of foam cells forming
And atherosclerotic plaques forming
What happens to mature HDL? (3)
Taken up by liver via specific receptors
Cells that require more cholesterol - utilise scavenger receptors to get cholesterol out of HDL
HDL can exchange cholesterol ester for triacylglyceride in VLDL - via cholesterol exchange transfer proteins
What is hyperlipoproteinaemia?
What is the cause? (2)
How many classes?
What are the defects in?
Raised plasma level of one of more lipoprotein class
Over production or under removal
6
Enzymes, receptors, apoproteins
What is a hypercholesterolaemia?
High levels of cholesterol in the blood
What are three clinal signs of hypercholesterolaemia?
Xanthelasma - yellow patches on eyelid
Tendon xanthoma - nodules on tendons
Corneal arcus - white circle around eye
What is atherosclerosis?
Disease of the arteries - deposition of fatty material on their inner wall
State the steps of LDL causing a stroke or myocardial infarction
- Oxidised
- Engulfed by macrophage
- Foam cells accumulate in intima of blood vessel wall - fatty streak
- Fatty streak builds up - atherosclerotic plaque
- Encroaches on lumen of artery
- Platelets activated - acute thrombosis
Treatment of hyperlipoproteinaemia (5)
- reduce cholesterol and saturate lipids in diet
- increase fibre in diet (binds to cholesterol in GI tract)
- increase exercise and stop smoking
- inhibit HMG-CoA reductase (reducing cholesterol synthesis)
- bind bile salts to GI tract - liver will produce more bile acids - using more cholesterol
How would you inhibit cholesterol production?
Inhibit HMG-CoA reductase
Using statins
