23. Lipoproteins Flashcards
What composition are most of the fatty acids that we ingest?
TAG are hydrophobic - how are they transported in the blood?
How is the transport of dietary and liver TAG different?
90% are triacylglycerol, and remainder = chol, chol ester, phospholipid and free FA
Packaged into lipoproteins, using cholestrol and proteins (apoproteins)
Dietary = packaged chylomicrons. Liver = TAG made in liver and released as VLDL (to peripehry, other lipoproteins are derived from it)
What do lipoproteins transport?
Describe the composition of a lipoprotein.
Whar are the 2 types of apoproteins?
What is the role of apoproteins?
Cholesterol, phospholipids, TAG, some vitamins (A, E)
Cholestrol esters and TAG in hydrophobic core, outer layer (hydrophilic) = phospholipids, free cholesterol and apoproteins, which differ between lipoprotein type
Embedded (e.g. apoB) or loosely bound (e.g. apoC)
Control fate of lipoprotein, interact with cellular receptors, activate/inhibit enzymes, allow lipoprotein to be loaded/unloaded at a point
Which apoproteins control the metabolism of LDLs and chylomicrons?
What does apoE and apoC do?
What is the major component of: chylomicrons, VLDL, IDL, LDL and HDL?
ApoB100 controls LDL metabolism, apoB48 controls chylomicron metabolism (truncated form)
ApoE: control receptor binding of remnant particles (i.e. removing them from blood), apoC: enzyme inhibitor
TAG, TAG, TAG + chol, Chol (esters), Protein
How does VDL become LDL, and what does LDL do?
What does HDL mainly contain, and what does it do?
What is lipoprotein lipase (LPL)?
What activates LPL?
As VLDL delivers material to peripheral tissue, there’s a change in density -> becomes IDL which can be converted to LDL by liver. LDL delivers cholesterol esters to peripheral tissues. “Bad lipoproteins”.
ApoC and apoE. Scavenges cholesterol from peripheral tissues and converts it to cholesterol esters, which are then distributed to other lipoproteins/liver. “Good lipoproteins”.
On endothelium adjacent to target cells, degrades TAG in chylomicrons and VLDL, and releases free FA and glycerol for uptake by adjacent cells.
ApoC2
Describe the ‘journey’ of a chylomicron.
How does lipoprotein lipase activity differ in times of plenty (i.e. after a meal) and starvation?
Chylomicron (apoB48 mainly, some A) takes TAG and chol from gut -> blood -> interact with HDL and take up apoCII and E from it -> C allows it to deliver its contents to peripheral/adipose/muscle tissue etc. -> chylomicron remnant: E allows it to be taken up by liver and disposed of
Times aplenty: LPL activity high in adipose tissues, chylomicrons delivered to adipose tissue -> store as fat or etherication. Chylomicron t1/2 = <1hr
Times of starvation: LPL activity high in muscle tissues, VLDL feed fats into beta oxidation in muscle to be used as fuel
Describe lipoprotein metabolism (VLDL, the 2 routes of IDL, and HDL).
VLDL prod in liver containing mainly apoB100, interact with HDL in blood, HDL transfters apoE and apoC to VLDL. ApoCII allows VLDL to deliver chol/TGL to peripheral tissues, changes density as it unloads -> IDL, carries on unloading TGL and exchanging apo with HDL, becomes-> LDL (no TGL left, only chol) -> taken up by peripheral tissues to deliver chol -> taken up by liver using apoB100
IDL can also be taken up by liver and transformed by HTGL (hepatic TAG lipase) into chol-rich LDL (containing apoB100). Lacks apoE so remains in circ longer and are taken up by liver (80%) or peripheral tissues.
HDL -> takes excess chol from peripheral tissue -> back to liver -> taken up by apoA1 receptor -> disposal in bile
What is cholestrol used for in the body?
Describe the 2 ways cells can synthesise cholestrol.
What transcription factor regulates this process?
Cell membranes, precursor of steroids and bile acids. Most cells can synthesise it.
1) LDL uptake via LDL (apoB/E) receptor on plasma membrane -> cholestrol released and esterified in cell
2) Glucose uptake -> acetyl CoA -> HMG CoA -> cholesterol (last step via HMG Co reductase. (when glucose plentiful!)
SREBP2 regulates expression of HMG-CoA reductase and the LDL apoB/E receptor b/c don’t want too much chol in cell. (Rates of receptor mediated endocytosis linked to how much chol in periphery)
How are HDL formed?
What does HDL do?
Are LDL and HDL risk factors for CVD?
What things elevate HDL levels?
Assembled in liver and intestine as lipid-poor particles (pre-b HDL) containing mainly apoAI
HDL scavenges free chol from e.g. cell membranes via ABCA1 transporter (membrane protein) and esterifies it to chol esters. Transports cholestrol from peripheral tissues -> liver for disposal. Binds to scavenger receptors in liver and transfers chol to the cell membrane. Redundant parts of HDL return to blood for next cycle.
LDL is, HDL is cardioprotective. Risk best expressed as HDL/LDL ratio.
Moderate alcohol consumption, regular aerobic exercise
What is linked to atherosclerosis?
How does LDL promote formation of atherosclerotic plaques?
High TAG levels (and thus risk of CHD of stroke). Dyslipidaemia common in diabetes. Risk of this is lower than high LDL:HDL - high LDL levels = longer it stays in blood more chance of damage from oxidation -> interact with things that aren’t LDL receptor -> taken up into cells, no feedback loop!
Oxidised LDL (free radicals), generated by smoking and diabetes, bind to scavenger receptors, rather than the LDL receptor, in macrophages. Scavenger receptors are not feedback regulated by chol, so macrophages = lipid laden = foam cells -> fatty streaks in arterial walls -> plaque
LDL stays in blood longer than HDL
How do statins work?
How does cholestryamine work?
What are the drawbacks?
Inhibit HMG CoA synthase - an enzyme on the pathway of cholestrol synthesis. Statins are chemically similatr to HMG-CoA = cooperative inhibitor. If statins can’t make chol then need to take more up so amount of LDL in blood drops.
Binds bile acids in gut preventing enterohepatic circulation. Reduce amount of bile in gut so body thinks needs more bile so produces more HDL. Liver wants more HDL so scavenges more from peripheral tissue.
Anything dependant on bile for digestion/absorption = problem so reduced uptake of fats and fat soluble vitamins (so need supplements). SE: GI effects mainly e.g. nausea, flatulence, bloating. 8-15% reduction in LDL but also rises TAG conc. Drug not systemically absorbed so safety.
NB. Finland, via public health measures, reduced serum chol and CVD deaths.
