Lipid transport Flashcards
What lipids are important signalling molecules?
Diacylglycerols
Plasma concentration range of total cholesterol
<5 mmol/L
Plasma concentration range of total lipids
4000-8500 mg/L
What polar head group is the most common in phospholipids?
Choline- phosphatidylcholine
What phospholipid head group is important in cellular signalling?
Inositol- phosphatidylinositol
How is cholesterol obtained?
Some from diet but mainly synthesised in liver
What steroid hormones is cholesterol the precursor of (4 things)?
- Cortisol
- Aldosterone
- Testosterone
- Oestrogen
What enzymes are used to esterify cholesterol to make cholesterol esters (2 things)?
- LCAT
- Acyl~CoA: cholesterol acyltransferase
What do lipoproteins consist of (4 things)?
- Peripheral apolipoproteins
- Integral apolipoproteins
- Phospholipid monolayer with small amount of cholesterol
- Cargo: triacylglycerol, cholesterol esters, fat soluble vitamins
What are the 5 distinct classes of lipoproteins?
- Chylomicron (mainly dietary fat transportation)
- VLDL
- IDL (intermediate)
- LDL (bad cholesterol)
- HDL (good cholesterol)
Which lipoproteins are main carriers of fat (2 things)?
- Chylomicron
- VLDL
Which lipoproteins are main carriers of cholesterol esters (3 things)?
- IDL
- LDL
- HDL
Apolipoproteins key points (5 things)
- Proteins
- 6 major classes (A,B,C,D,E & H)
- Structural role of packaging water insoluble lipid
- Co-factor for enzymes
- Ligands for cell surface receptors
Chylomicron metabolism (7 things)
- Loaded in small intestine and apoB-48 added before entering lymphatic system
- Travel to thoracic duct which empties in left subclavian vein
- Acquire apoC & apoE once in blood
- apoC binds lipoprotein lipase on adipocytes & muscle
- Released fatty acids enter cells depleting chylomicron of content
- When ~20%, apoC dissociates and chylomicron becomes chylomicron remnant
- Return to liver: LDL receptor on hepatocytes binds apoE and remnant taken up via receptor-mediated endocytosis
VLDL metabolism (4 things)
- apoB100 added during formation & apoC + apoE added from HDL particles in blood
- VLDL binds to LPL on muscle endothelium
- Starts to become depleted of triacylglycerol
- Used as energy in muscle but stored as fat in adipose
IDL & LDL metabolism (4 things)
- As TAG content of VLDL drops, they dissociate from LPL enzyme complex and return to liver
- If drops to ~30% it becomes a short-lived IDL particle
- IDL particles can be taken up by liver or rebind to LPL enzyme to further deplete TAG content
- When ~10% apoC & apoE lost and becomes LDL (high cholesterol)
Function of LDL
To transport cholesterol- not efficiently cleared by liver though as don’t have apoC or apoE
Clinical relevance of LDL (3 things)
- Half-life much longer so more susceptible to oxidative damage
- Oxidised LDL taken up by macrophages transforming them into foam cells
- Can build up and contribute to atherosclerotic plaques
LDL entering cells via receptor mediated endocytosis (4 things)
- LDL receptors on cells
- apoB100 acts as a ligand
- Receptor/LDL complex taken in by endosomes in endocytosis
- Fuse with lysosomes for digestion to release cholesterol & fatty acids
HDL metabolism- synthesis (3 things)
- Nascent HDL synthesised by liver & intestine
- Can also bud off from chylomicrons
- Free apoA-I can also acquire cholesterol & phospholipid to form nascent-like HDL
HDL metabolism- maturation (2 things)
- Accumulate phospholipids and cholesterol from cells lining blood vessels
- Hollow core progressively fills and particle takes on more globular shape
HDL metabolism- reverse cholesterol transport (3 things)
- Can remove cholesterol from cholesterol-laden cells and return to liver
- Reduces likelihood of foam cell formation
- ABCA1 protein facilitates this
HDL metabolism- fate of mature HDL (3 things)
- Mature HDL taken up by liver via specific receptors
- Cells needing more cholesterol can use scavenger receptor to obtain it from HDL
- Can also exchange cholesterol esters for TAG with VLDL via action of CETP
Hyperlipoproteinaemias key points (3 things)
- Caused by over-production or under-removal
- Defects in enzymes, receptors & apoproteins
- 6 main types
