Flashcards in Lipoprotein Lecture (Lecture 3) Deck (31):
Exogenous pathway involves ...
Endogenous pathway involves ...
mainly low density lipoproteins
Reverse transport involves ...
Food with dietary cholesterol?
What happens to dietary cholesteryl esters in the lumen?
In the lumen of the intestine, dietary cholesteryl esters are hydrolyzed, and cholesterol, along with other sterols, enter mixed micelles that contain bile salts, fatty acids, and monoglycerides
Where in the GI tract are sterols absorbed?
Epithelial cells of the jejunum take up sterols from the lumen of the intestine rather indiscriinately via binding to NPC1L1, followed by endocytosis
What is NPC1L1?
An abbreviation of Niemann-Pick C1-like protein 1. Found on the gastrointestinal tract epithelial cells; critical mediator of sterols absorption.
Describe the absorption of cholesterol
The intestine incorporates cholesterol and cholesteryl esters into chylomicrons, and after loss of associated triglycerides, the cholesterol-rich chylomicron remnants enter the liver
Synthesized in the liver and reside on HDL. It is an essential cofactor for lipoprotein lipase (LPL)
** lipoprotein lipase activator **
(Note: not a cofactor for hepatic lipase)
lipoprotein lipase inhibitor
(1) acquired by chylomirons from HDL
(2) serves as the ligand for a receptor-mediated clearance by the liver
** Remnant receptor binding (serves as the ligand for a receptor-mediated clearance of the chylomicron remnants by the liver) **
Explain the receptor-mediated clearance by the liver by binding to apolipoprotein E?
Apolipoprotein E on chylomicron remnants binds to the LDL receptor-related protein 1 (LRP1) on hepatocytes, and the remnants enter via endocytosis
What is the function of lipoprotein lipase?
cleaves fatty acids from the triacylglycerols present in the anhydrous core in lipoproteins, thereby diminishing the TAG content of the lipoprotein
What do triacylglycerides degrade into (i.e. the effect of lipases)?
FFAs + glycerols; lipases hydrolyze triglycerides inside chylomicrons or VLDL to fatty acids and glycerol
(1) lipoprotein lipase
(2) hepatic lipase
Where are the lipases located?
lipoprotein lipase: on the walls of blood capillaries of tissues
hepatic lipase: in capillaries of the liver
Why are lipases located on capillaries?
Allows free fatty acids to return to circulation
How does lipoprotein lipase work?
(1) Lipoprotein lipase is attached to glycosaminoglycans on the endothelial cell (remember lipase is found on capillary wall which is made of epithelial cells)
(2) Lipoprotein lipase interacts with chylomicrons or VLDL to catalyze the hydrolysis of triacylglycerols (apolipoprotein CII on the lipoproein serves as a cofactor for lipoprotein lipase)
Where do the fatty acids go?
80% of the fatty acids are taken by adipose tissue, heart and muscle and 20% are returned back to the liver.
Uses of fatty acids?
(1) storage (by adipose cells)
(2) used for energy (by muscles)
(3) transported by serum albumin until uptake occurs
(1) has both a phospholipase and triglyceride hydrolase activity
(2) synthesized by hepatocytes and is present primarily on liver endothelial cells
(3) hydrolyzes triglycerides and possibly excess surface phospholipids in the final processing of chylomicron remnants and the processing of IDL to LDL
(4) participates in the conversion of HDL2 to HDL3 by the removal of triglyceride and phospholipid HDL2
Where are chylomicrons synthesized?
Purpose of chylomicrons?
transport dietary lipids; dietary TAGs are delivered to adipose and ther peripheral tissues
Characteristics of chylomicrons?
98% lipid, large sized, lowest density
Apolipoproteions on chylomicrons?
Apo B-48 (provides an indicator of intestinal derived lipoproteins in circulation), Apo C-II, Apo-CIII, and Apo E
Fasting blood sample and concentration of chylomicrons
a fasting blood sample is taken in order to not affect the results by the present of "contaminating" chylomicrons. Will clear from the blood within a few hours of a meal (i.e. half-life for a given particle is expressed in terms of minutes)
What does dietary cholesterol inhibit?
Dietary cholesterol inhibits cholesterol synthesis by the liver
What apoliprotein and lipids are contain in nascent chylomicron?
Apoprotein B48 and a large cargo of triacylglycerol (with a little cholesterol, cholesterol ester and phospholipid)
What apolipoprotein do chylomicrons receive from HDL?
Apoproteins E and CII
How do chylomicrons becomme chylomicron remnants?
As triacylglycerol is lost; TAGs are lost because lipoprotein lipase hydroxylses TAGs to liberate free fatty acids which diffuse into the local tissues