Flashcards in Lecture 7 - Lipid Control in Health and Disease Deck (31):
How were different lipoproteins named?
By where they banded on an equilibrium density gradient centrifuge tube.
Implication of greater lipoprotein density
More protein, less lipid
Shape of lipoproteins
What are lipoproteins bound by?
A phospholipid monolayer
1) ApoB-100 protein
2) Phospholipid monolayer with unesterified cholesterols
3) Core of triaceylglycerols and cholesterol esters
When does risk of heart attack significantly rise w/r/t blood cholesterol level
1) Apolipoproteins (B-48, C-II, C-III)
2) Less cholesterol than LDL
3) More protein than LDL
Where are chylomicrons formed?
Role of chylomicrons
Carry TAGs from diet to tissues via the lymphatics and blood
Cholesterol form on the surface of lipoproteins
Free (unesterified) cholesterol
Are chylomicrons more or less dense than VLDL?
Lipoproteins that primarily carry TAGs in the blood
Lipoproteins that primarily carry cholesterol in the blood
Three lipid transport systems
3) Reverse cholesterol transport
Exogenous lipid transport
1) Dietary fats broken down into free fatty acids, mono- and diacylglycerols by intestinal lipases (bile salts emulsify)
2) Breakdown products are taken up by mucosa, reformed into TAGs and incorporated into chylomicrons
3) Chylomicrons move through bloodstream and lymphatics into tissues
4) ApoC-II on chylomicron activates lipoprotein lipase on capillary wall. Lipoprotein lipase converts TAGs to free fatty acids and glycerol
5) Fatty acids enter cells, are either oxidised for energy or reesterified for storage
6) Chylomicrons depleted of TAGs (chylomicron remnants) are taken in the blood to the liver, where they are taken up by RME
Endogenous lipid transport
1) VLDL assembled in ER of hepatocytes on ApoB-100 scaffold
2) ApoE and ApoC-II associate with VLDL in the blood.
3) Lipoprotein lipase (activated by ApoC-II) converts TAGs to FFAs. This converts VLDL to IDL (intermediate-density lipoprotein).
4) ~50% of IDL taken up by liver via LDL receptor that recognises ApoE on IDL. ~50% of IDL sheds ApoE, becomes LDL.
5) ~70% of LDL is taken up by liver via LDL-R, ~30% enters muscle, adipocytes, adrenal glands.
How does ApoB-100 help form VLDL?
Has binding sites for microsomal transfer protein (MTP) necessary for formation of VLDL
Reverse cholesterol transport
1) HDL starts as a disc of ApoA-1 (protein) and phospholipid
2) Free cholesterol is esterified, incorporated into HDL3
3) More esterified cholesterol binds to HDL, forming HDL2
4) CETP assists in the exchange of esterified cholesterol from HDL with TAGs from LDL and VLDL.
5) HDL interacts with SR-B1 in the liver, delivers TAGs to the liver.
Why might high HDL levels correlate with less heart disease?
HDL in blood picks up excess free cholesterol from arterial walls, converts them to cholesteryl esters, delivers them to the liver where they are converted to bile.
Where is ApoA-1 formed?
In the liver and intestine
Protein disc that forms core of HDL
Medications that can increase blood TAGs
1) Beta blockers
3) Oestrogen replacement
Medications that can decrease TAG clearance from blood
1) Beta blockers
2) Protease inhibitors
What effect does hyperthyroidism have on TAG levels in blood?
Reduces TAG clearance, increases TAG formation
Genetic factors that can lead to increased blood TAG levels
1) ApoB-100 mutations can lead to increased VLDL
2) Lipoprotein lipase or ApoC-II mutations can reduce TAG breakdown
Can cause atherosclerotic plaques
Examples of dislipidaemias
2) Increased LDL
4) Decrease in HDL
How can metabolic syndrome cause dyslipidaemias?
Alterations to HDL and LDL particles.
Abnormal LDL are more atherogenic. Small, dense, TAG-rich, oxidised, glycated.
HDL in metabolic syndrome and T2DM
1) Hypertriglyceridaemia can lead to increased HDL catabolysis
2) increased glycation of HDL could interfere with cholesterol efflux from cells and cholesterol reverse transport
How can hypertriglyceridaemia lead to increased HDL catabolysis?
With more TAGs, CETP transfers more TAGs from VLDL and LDL to HDL.
TAG-rich HDL is degraded more by hepatic lipase