Lipoprotein Lecture (Lecture 3) Flashcards
Exogenous pathway involves …
chylomicrons
Endogenous pathway involves …
mainly low density lipoproteins
Reverse transport involves …
HDL
Food with dietary cholesterol?
animals only
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
Apolipoprotein C-II?
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)
Apolipoprotein CIII?
lipoprotein lipase inhibitor
Apolipoprotein E?
(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
Two lipases
(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
Hepatic Lipase
(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?
small intestine
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
