Lipid transport Flashcards
(32 cards)
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
Describe the role of reverse cholesterol transport in preventing atherosclerosis.
- 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
26
Describe the fate of mature HDL
- 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
What are hyperlipoproteinaemias
- raised plasma levels of ≥ 1 lipoprotein classes
- caused by over-production or under-removal
28
Types of hyperlipoproteinaemias
- 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
Clinical signs of hypercholesterolaemia
- 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
30
Describe how raised serum LDL is associated with Atherosclerosis.
1. oxidised LDL recognised by macrophages
2. foam cells (lipid laden macrophages) accumulate in intima of blood vessel walls
- forms fatty streak
3. fatty streak evolves into atherosclerotic plaque
4. grows & encroaches on artery lumen
- angina
5. rupture
- triggers acute thrombosis (clot) by activating platelets & clotting cascade
> stroke
=> myocardial infarction
31
• Explain the first response in how hyperlipoproteinaemias may be treated.
- diet
- reduce cholesterol & saturated lipids
- increase fibre intake
- lifestyle
- increase exercise
- stop smoking to reduce CVD risk
32
. Explain how hyperlipoproteinaemias may be treated if initially treatment is unresponsive
- 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
