Sources of Cholesterol
Rate limiting enzyme of cholesterol production
Fates of Cholesterol
Lipid and cholesterol transport systems make use of the same ____.
Lipid and cholesterol transport systems make use of the same lipoprotein transporters.
Chylomicrons deliver dietary fat that is ____; VLDL delivers fat that is ____.
Chylomicrons deliver dietary fat that is absorbed in the intestine; VLDL delivers fat that is produced by the liver.
enterohepatic circulation of bile acids
Bile acids are excreted from the gall bladder, used to emulsify fat in the gut, and then many are reabsorbed and delivered back to the liver.
Consequences of elevated LDL
Cholesterol and Cholesteryl esters
Schematic of LDL
Scale of Lipoproteins
A lipoprotein stripped of all its lipids.
Core protein of HDL. Activates LCAT, the enzyme that triggers reverse cholesterol transport from cells to HDL
ApoB48 and B100 relationship
These proteins are both expressed from the same gene, and are made by the small intestine and liver, respectively
In the liver, the full length apolipoprotein is made (100% of full length, so it is called ApoB100). This protein acts as a scaffold for the VLDL particle, and thus is also found in the derivative particles IDL and LDL. It acts as the major binding site for the LDL receptor and is thus responsible for uptake of the LDL particle by the liver.
In the small intestine, a shorter version (48% of full length) of ApoB is produced (hence ApoB48). This protein acts as the scaffold for a chylomicron. Since it lacks the C-terminal region of ApoB100, it cannot bind the LDL-receptor, and thus chylomicron remnants rely primarily on ApoE for uptake by the liver.
Activates lipoprotein lipase
Triggers clearance of some VLDL particles and all chylomicron remnants.
Apo C and E relationship
Secreted by the liver and intestine into the blood stream, where they then bind the nascent lipoprotein particles.
Apo E and C can also be transferred between HDL, VLDL and chylomicrons.
Common Pathway for Lipoprotein Production
microsomal triglyceride transfer protein
Responsible for loading VLDL (liver) and chylomicrons (intestine) with triacylglycerides within the ER as the apolipoproteins are being translated. This step is called lipidation.
Enterocytes secrete chylomicrons into ___. Hepatocytes secrete VLDL into ___.
Enterocytes secrete chylomicrons into lacteals, which then drain into local lymphatics and eventually enter venous circulation via the thoracic duct. Hepatocytes secrete VLDL into the bloodstream directly.
Life of a chylomicron
Fatty acid and glycerol absorption and packaging into chylomicrons (within enterocytes)
Niemann-Pick C1–like 1 (NPC1L1) protein
A cholesterol transporter located within the apical membrane of an enterocyte. Responsible for dietary cholesterol absorption.
Small molecule inhibitor of NPC1L1. Prevents/lessens dietary cholesterol absorption.
Dietary cholesterol absorption diagram
Lacteals and Gut Lymphatics
Location of the cysterna chyli
Just posterior to the pyloric sphinctre and just right of the abdominal aorta.