What are the two interconnected cycles of lipoprotein metabolism centered on the liver?
Endogenous and exogenous
What are lipoproteins and what do they do?
Non-covalent complexes of lipids and proteins; carry lipids through the bloodstream
What is purpose of particle density? What are the defining characteristics?
It is used to classify lipoproteins.
Difference in composition, structure, and function.
Protein constituents of lipoproteins have what 2 roles?
structural and functional
What is the shape of lipoproteins and what structures are on the surface?
Spherical with proteins, cholesterol, and phospholipids on the surface
What makes up the inside of the sphere?
Non-polar lipids
What are the major classifications of lipoproteins, and how are they determined?
Determined based upon density
Chylomicrons, VLDL, ILDL, LDL, HDL
True/False: The lipoproteins have a MONO-layer of mainly amphipathic lipids
True
Which Apoproteins are embedded in the monolayer?
Apo B100 and Apo B48
What carries free fatty acids?
Albumin
Which lipoprotein has the smallest density? Why?
Chylomicrons; they are filled with TAGs
Which lipoproteins are the most dense? Why?
HDLs; they are full of esterfied cholesterol
Which lipoproteins are the largest in diameter? Which are the smallest?
Chylomicrons are the largest; HDL is the smallest
Which lipoprotein has the highest percent of cholesterol and cholesterol ester?
LDL
What is the purpose of bile salts?
They emulsify dietary fats and increase surface area of the lipid to speed up digestion.
What do intestinal enzymes breakdown?
Dietary TAG, cholesterol esters, and phospholipids
What are the 3 main intestinal enzymes for digestion of lipids and what is the 1 helper enzyme?
Pancreatic lipase, Cholesterol esterase, and Phospholipase
Helper: Colipase
What is the purpose of pancreatic lipase?
Cleaves ester bonds in dietary TAG
What is the purpose of Colipase?
Helps pancreatic lipase attach to micelles.
What is the purpose of Cholesterol esterase?
Hydrolyzes cholesterol esters
What is the purpose of Phospholipases?
Breaks down phospholipids
Where are TAGs and cholesterols transferred?
They are transferred across the intestinal mucosa
What happens to TAGs and cholesterol once inside the enterocyte?
TAG: are reformed
Cholesterol: esterfied with fatty acids
What is required to bring TAGs into the chylomicrons?
Microsomal Triglycerides Transferase
Once formed, where are chylomicrons transferred and where to they go from there?
Lymphatic circulation then it goes to the blood stream (L Subclavian Vein)
What enzyme in the blood stream is activated by Apo CII in the Chylomicrons and VLDs?
Lipoprotein lipase
What does lipoprotein lipase do to the Chylomicrons?
They release fatty acids from the Chylomicrons
What happens to the released fatty acids from the Chylomicrons?
They enter cells and are repackaged into VLDLs.
What happens to Chylomicron remnants?
They are degraded by the liver.
True/False: Chylomicrons release cholesterol to the tissues
FALSE!!! They DO NOT release cholesterol to tissues.
Chylomicrons are carriers of lipids from what area?
The GI
Where and when are chylomicrons synthesized?
intestinal epithelium; after a meal
Of what are the chylomicrons the principal carriers?
dietary lipids and fat-soluable vitamins (D,A,K,E)
What is the purpose of chylomicrons?
Deliver lipids to tissues.
Where would you NOT find chylomicrons?
normal fasting plasma
What apoproteins are in chylomicrons?
Apo B-48 (added upon formation)
A-I, C-II, E (added after entering the blood from HDL)
Where and from what are VLDLs made?
Liver; biosynthesis of FA and chylomicron remnants.
What is the main purpose of VLDLs?
They are the main carrier of endogenously synthesized TAGs to tissues
Which apoproteins are in VLDLs?
Apo B-100 (Added upon synthesis)
C-II, and E (Added from HDL in the blood stream)
Where and from what are LDLs formed? What is the intermediate structure?
They are formed from VLDLs in the circulation; ILDL
What is the purpose of LDLs?
Transport cholesterol to the tissues
Which Apoprotein is contained in LDL? How does that differ from ILDL?
ILDL has Apo B-100, C-II, and E, but returns the Apo C-II and Apo E to HDL. It is then LDL and only contains Apo B-100
HDL is the smallest lipoprotein particle but most abundant, what is its function?
It takes cholesterol from the tissues back to the liver for excretion. It also distributes cholesterol to other lipoproteins (reverse cholesterol transport).
Which apoproteins does HDL contain?
Apo A-I and A-II
Where is HDL made?
Liver and sm. intestines
What is the purpose of Apoprotein A-1?
Activates LCAT and binds HDL receptor
HelLcat esterfies
What is the function of Apoprotein B-48?
It is involved in the formation of chylomicrons (embedded within the monolayer)
What is the function of Apoprotein B-100?
It binds LDL receptor (docking element)
What is the function of Apoprotein C-II? And which lipoproteins does this effect?
It activates lipoprotein lipase (LPL); chylomicrons and VLDLs
What is the function of Apoprotein E?
Recognition of the LDL receptor (docking protein to remove the remnants of chylomicrons)
What protein is involved in reverse cholesterol transport (aside from HDL)?
Cholesterol ester transfer protein (CETP) - it mediates the exchange of cholesterol from HDL to VLDL, ILDL, and LDL
What is the function of lipoprotein lipase?
It delipidates VLDL and the chylomicrons at the capillary surface
What is LCAT?
It is a peripheral protein that is made in the liver and secreted in the blood.
What can happen to LDL in the presence of ROS?
It can not get rid of fat and produces fatty streaks in the coronary vessels, leading to plaque build-up.
What is the shape of HDL prior to esterification by LCAT?
It begins as a disc, but as cholesterol esters are added, it becomes more dense and spherical.
What type of receptor is an LDL receptor?
glycoprotein
What is ACAT (aceyl-CoA cholesterol acyl transferase)?
It transfers a FA from fatty acyl CoA to cholesterol producing a cholesterol ester, which is then stored.
What is another activator of lipoprotein lipase?
Insulin
Once the chylomicron is deplipidated, which peripheral apoprotein is returned to HDL? And what is the function of the remaining peripheral apoprotein?
Apo C-II is returned to HDL. Apo E remains to bind to receptors on the liver for endocytosis.
