Lipoprotein Physiology Flashcards
What are the relative polarities of cholesterol esters, triglycerides, un-esterified cholesterol, and phospholipids?
Un-esterified cholesterols and phospholipids are more polar than cholesterol esters and triglycerides.
Name the five classes of lipoproteins
Chylomicrons Very Low Density Lipoproteins Remnant Particles/Intermediate Density Lipoproteins Low Density Lipoproteins High Density Lipoproteins
Where are chylomicrons made, what is their ratio of triglycerides to cholesterol, and what physical effect do they cause?
Chylomicrons are made in the GI tract from dietary fat.
They have >10:1 Triglyceride to cholesterol ratio (matches the dietary intake of each)
They are responsible for the rise in serum triglyceride levels after a meal
Where are very low density lipoproteins made, what is their ratio of triglycerides to cholesterol, and what physical function do they have?
VLDL are made in the liver.
Triglyceride:Cholesterol = 5:1
VLDL deliver triglycerides to peripheral tissues between meals but are made at higher levels during meals. Participate in “Basal triglyceride production”
What are Remnant Particles/Intermediate Density Lipoproteins, what is their Tg:Ch ratio, and what physical effects do they have?
RP/IDL are the remnants of VLDLs and chylomicrons after they have supplied their Tg to peripheral tissues and their Tg:Cholesterol ratios have decreased. They are smaller, with roughly 1:1 Tg:Ch ratios and are atherogenic.
What are Low Density Lipoproteins, what is their Tg:Ch ratio, and what physical effects do they have?
LDLs are produced by the metabolism of VLDLs, have more cholesterol than Tg (Tg:Ch less than 1:1), and are very atherogenic. The less Tg they have, the more atherogenic they are. They are cleared by the liver
What are High Density Lipoproteins and what is their physical role?
HDLs are the “trash trucks” of lipid metabolism. They collect cholesterol in the periphery and transport it to the liver, provide a source of phospholipids, and exchange Tg and apt-protein with other particles. HDL has an inverse correlation with atherosclerotic risk.
What are the lipoproteins, apo-proteins and enzymes involved in the chylomicron pathway and where does each come from?
Lipoproteins:
Chylomicrons
Remnant particles
HDL
Apo-proteins:
B48 - Intestinal epithelial cells
C2 - HDL in circulating blood
E - HDL in circulating blood
Enzymes: Lipoprotein Lipase (LPL) - Endothelial cell surface (C2 is a cofactor for LPL)
Summarize the chylomicron pathway
Dietary fats are hydrolyzed to FFA and monoacylglycerol and taken up by intestinal epithelium where it is repackaged into Tg along with cholesterol and apo-protein B48. Now called a chylomicron, it moves into the gut lymphatics and then the general circulation where it receives apo-proteins C2 and E from HDLs. At the surface of endothelial cells, Tg on the chylomicron is broken down by LPL which needs C2 as a cofactor (absence of C2 prevents breakdown of Tg-rich lipoproteins and leads to hypertriglyceridemia). Normal catabolism of chylomicrons via LPL produces Remnant Particles that are taken up in the liver. Both particles are normally absent in the fasting state, hence the need for fasting to accurately test Tg levels.
What are the lipoproteins, apo-proteins and enzymes involved in the VLDL pathway and where does each come from?
Lipoproteins: VLDL VLDL-remnant particles LDL HDL
Apo-proteins:
B100
C2
E
Enzymes:
LPL
LDL-receptors
Summarize the VLDL pathway
VLDL is synthesized by the liver with Tg:Ch of 5:1 and one B100 app-protein. As with chylomicrons, VLDL acquires C2 and E from HDL in the circulation, and are metabolized by LPL (plus C2) on endothelial cells, forming VLDL remnant particles and subsequently LDL. LDL is roughly 10% Tg and 45% cholesterol, and is highly atherogenic. LDL retain the B100 marker of the VLDL and are taken up by LDL receptors, mostly in the liver, where their cholesterol contents regulates further synthesis. Defective LDL receptors leads to very high levels of circulating LDL and increased risk of atherosclerosis.
What are the lipoproteins, apo-proteins and enzymes involved in the HDL pathway and where does each come from?
Lipoproteins:
HDL - liver and intestine
VLDL - liver
Chylomicrons - Intestine
Apo-proteins:
ApoA1 - liver
C2 - liver
E - liver
Enzymes
ABC-A1 cassette
Lecithin Cholesterol Acyltransferase (LCAT)
Cholesterol Ether Transfer Protein (CETP)
Summarize the HDL pathway
HDL containing ApoA1 is produced in the liver and intestines, circulates in the plasma and picks up free cholesterol in peripheral tissues via diffusion and facilitated transport via ABC-A1 cassette. HDL “traps” free cholesterol by converting it to cholesterol esters with LCAT and phospholipids (cholesterol-fatty acid ester). HDL transfers cholesterol esters to VLDL in exchange for Tg via CETP. In this way, HDL picks up cholesterol and Tg in the periphery and transfers them to the liver, where it is absorbed by hepatocytes. HDL also acts as a store for C2 and E apo-proteins for use by other lipoproteins.
What are the three known functions of apo-proteins and examples of each?
1 - Structural backbone of lipoproteins
apoB48 - chylomicrons
apoB100 - LDL and VLDL
apoA1 - HDL
2 - Enzymatic cofactors
apoC2 - cofactor for LPL
3 - Ligands for receptors
apoB100 - ligand for LDL receptor
apoE - ligand for Remnant receptor
What role does the ABC A1 enzyme play and what occurs in a deficiency?
ATP Binding Cassette (ABC) A1 helps transport cholesterol from peripheral tissue to apoA1 (HDL). Tangier’s disease occurs in people who lack this enzyme cannot remove cholesterol from tissues and suffer from premature atherosclerosis. Classically present with “orange tonsils” which reflect cholesterol accumulation in the lymphatics.
