Lipid transport Flashcards
1
Q
• Describe how lipids are transported in the blood. (lipolysis)
A
- TAG in adipose catalysed by hormone sensitive lipase
- glycerol
- travels to liver
- utilised as carbon store for gluconeogenesis
- fatty acids
- travels complexed with albumin to muscle & other tissues for β-oxidation
- glycerol
2
Q
Regulation of lipolysis
A
- glucagon & adrenaline
- phosphorylation
- activation of HSL (hormone sensitive lipase)
- insulin
- de-phosphorylation
- inhibition of HSL
3
Q
Plasma cholesterol concentration ranges
A
< 5mmol/L
4
Q
Phospholipid structure
A
- phosphatidylcholine
- choline head bonded to glycerol with phosphate group
- phosphatidylinositol (minor)
- inositol head bonded to glycerol with phosphate group
- role in cellular signalling
- inositol head bonded to glycerol with phosphate group
5
Q
What is the difference between a liposome & micelle
A
- liposome
- bilayer
- hydrophilic- micelle
- monolayer
- hydrophobic
- micelle
6
Q
Where is cholesterol obtained from
A
- mostly synthesised in liver
- some obtained from diet
7
Q
Uses of cholesterol
A
- membrane component
- modulates fluidity
- precursor of steroid hormones
- cortisol
- aldosterone
- testosterone
- oestrogen
- precursor of bile acid
8
Q
How is cholesterol transported around the body
A
as cholesterol esters
9
Q
Lipoprotein makeup
A
- peripheral apolipoproteins
- integral apolipoprotein
- phospholipid monolayer with small amount of cholesterol
- cargo
- TAG
- cholesterol ester (c linked to fa)
- fat soluble vitamins
10
Q
Peripheral apolipoprotein examples
A
- apoC
- ApoE
11
Q
Integral apolipoprotein
A
- apoA
- ApoB
12
Q
Classes of lipoprotein
A
- chylomicrons
- transport dietary fat
- VLDL (very low density lipoprotein)
- transports TAG made in the liver to other tissues
- IDL (intermediate density lipoprotein)
- short-lived intermediary produced when VLDL content is depleted to ~ 30%
- LDL
- produced when IDL contents depleted to ~ 10%
- HDL
- transport excess cholesterol from cells to liver
13
Q
Main carriers of fat
A
- chylomicron
- VLDL
14
Q
Main carriers of cholesterol esters
A
- IDL
- LDL
- HDL
15
Q
Function of apolipoprotein
A
- structural
- packaging water insoluble lipid
- functional
- co-factor for enzymes
- ligands for cell surface receptor
16
Q
Apoliproteins
A
- 6 major classes (A, B, C, D, E & H)
- apoB (VLDL, IDL, LDL) and apoAI (HDL) important
- either integral or peripheral
17
Q
Describe chylomicron metabolism.
A
- loaded into small intestine & apoB-48 added before entering lymphatic system
- travel to thoracic duct
- empties to left subclavian vein
- acquires apoC and apoE once in blood - apoC binds to lipoprotein lipase (LPL) on adipocytes & muscle
- fatty acids enter cells, depleting chylomicron’s fat content - when TAG reduced to ~ 20%, apoC dissociates
- chylomicron becomes chylomicron remnant - remnant returns to liver
- LDL receptor on hepatocytes bind to apoE
- remnant taken up by receptor mediated endocytosis - lysosomes release remaining contents for use in metabolism
18
Q
Describe VLDL metabolism.
A
- apoB100 added during formation in liver
- apoC and apoE added from HDL in blood
- VLDL binds to LPL on endothelial cells in muscle & adipose
- TAG depletes
- In muscle: released fatty acids taken up & used in energy production
- In adipose: fatty acids used for re-synthesis of TAG and stored as fat
19
Q
Lipoprotein lipase (LDL)
A
- hydrolyses TAG in lipoproteins
- requires ApoC-II as co-factor
- attached to surface of endothelial cell in capillaries
20
Q
Describe the features of LDL.
A
- lost apoC & apoE
- not efficiently cleared by liver
- liver LDL-receptor has high affinity for apoE
- not efficiently cleared by liver
- high cholesterol content
- transports cholesterol from liver to peripheral tissue
- tissues express LDL receptor
- take up LDL via receptor mediated endocytosis
- tissues express LDL receptor
- transports cholesterol from liver to peripheral tissue
21
Q
Clinical relevance of LDL
A
- half life in blood is longer than VLDL or IDLL
- more susceptible to oxidative damage
- oxidised LDL taken up by macrophages → foam cells
- contribute to atherosclerotic plaque formation
22
Q
Describe the process by which LDL is uptaken by receptor mediated endocytosis
A
- LDL receptor expressed on membrane
- apoB-100 on LDL acts as ligand for receptors
- expression controlled by cholesterol concentration in cell
- LDL complex taken in by endocytosis into endosomes
- Endosome fuse with lysosome for digestion to release cholesterol and fatty acids
23
Q
HDL synthesis
A
- by liver + intestine
- can also bud off chylomicrons & VLDL during digestion by LPL
- free apoAI can acquire cholesterol + phospholipids from other lipoprotein & cell membrane to form nascent-like HDL
24
Q
Maturation of HDL
A
- nascent HDL accumulate phospholipids & cholesterol from endothelial cells
- doesn’t require enzyme activity
25
Q
Describe the role of reverse cholesterol transport in preventing atherosclerosis.
A
- HDL can remove cholesterol from cholesterol-laden cells & return it to liver
- reduces likelihood of foam cells & atherosclerotic plaque formation
- facilitated by ABCA1 protein
- cholesterol converted to cholesterol ester by LCAT
- facilitated by ABCA1 protein
- reduces likelihood of foam cells & atherosclerotic plaque formation
26
Q
Describe the fate of mature HDL
A
- taken up by liver via specific receptors
- cells requiring additional cholesterol utilise scavenger receptor (SR-B1)
- obtains cholesterol from HDL
- HDL can exchange cholesterol esters for TAG with VLDL
- via action of cholesterol exchange transfer proteins (CETP)
27
Q
What are hyperlipoproteinaemias
A
- raised plasma levels of ≥ 1 lipoprotein classes
- caused by over-production or under-removal
28
Q
Types of hyperlipoproteinaemias
A
- I
- Chylomicrons in fasting plasma.
- No link with coronary artery disease.
- Caused by defective lipoprotein lipase
- IIa
- Associated with severe coronary artery disease
- Caused by defective LDL receptor
- IIb
- Associated with coronary artery disease.
- Defect unknown.
- III
- Raised IDL and chylomicron remnants.
- Associated with coronary artery disease.
- Rare
- Caused by defective apoE
- IV
- Associated with coronary artery disease.
- Defect unknown.
- V
- Raised chylomicrons and VLDL in fasting plasma.
- Associated with coronary artery disease.
- Cause unknown
29
Q
Clinical signs of hypercholesterolaemia
A
- high blood cholesterol
- cholesterol deposition in various areas of body
- xanthelasma
- yellow patches on eye lids
- tendon xanthoma
- nodules on tendon
- corneal arcus
- white/blue circle around eye
- common in older people, but indicative of disease in younger people
- xanthelasma
30
Q
Describe how raised serum LDL is associated with Atherosclerosis.
A
- oxidised LDL recognised by macrophages
- foam cells (lipid laden macrophages) accumulate in intima of blood vessel walls
- forms fatty streak - fatty streak evolves into atherosclerotic plaque
- grows & encroaches on artery lumen
- angina
- rupture
- triggers acute thrombosis (clot) by activating platelets & clotting cascade
> stroke
=> myocardial infarction
- triggers acute thrombosis (clot) by activating platelets & clotting cascade
31
Q
• Explain the first response in how hyperlipoproteinaemias may be treated.
A
- diet
- reduce cholesterol & saturated lipids
- increase fibre intake - lifestyle
- increase exercise
- stop smoking to reduce CVD risk
32
Q
. Explain how hyperlipoproteinaemias may be treated if initially treatment is unresponsive
A
- statins
- reduce cholesterol synthesis
- inhibiting HMG-CoA reductase - bile salt sequenstrants
- bind bile salts in GI tract
- forces liver to produce more bile acids using more cholesterol
