lipoprotein physiology

Question 1

List the relative polarities of cholesterol ester, triglyceride, un-esterified cholesterol and phospholipids

Answer 1

Cholesterol esters and triglycerides are non polar. Un-sterified cholesterol and phospholipids are more polar and are packaged with apo-lipoproteins to form lipoproteins.

Question 2

How is cholesterol removed from the body

Answer 2

bile excretion is the only method! Cholesterol is not consumed by oxidation

Question 3

elevated triglycerides can lead to…

Answer 3

pancreatitis

Question 4

List 5 classes of lipoproteins

Answer 4

chylomicrons, VLDL, IDL, LDL, HDL

Question 5

Describe the characteristics of chylomicrons

Answer 5

Made by GI tract from dietary fat. Large, >10:1 triglyceride to cholesterol

Question 6

Describe the characteristics of VLDL

Answer 6

Large, 5:1 tg to chol, made by liver, They are the source of “basal triglyceride production”. deliver triglyceride to peripheral tissues between meals, but are also made at lower levels in the post-meal period

Question 7

Describe the characteristics of IDL

Answer 7

Metabolic byproducts of the metabolism of chylomicrons and VLDL. Mid sized, equal amounts of tg and chol. Atherogenic

Question 8

Describe the characteristics of LDL

Answer 8

Produced from metabolism of VLDL. 45% chol, 10% tg.. Major cholesterol carriers in plasma Atherogenic- the less tg they contain the smaller, more dense and more atherogenic they are. Cleared by liver

Question 9

Describe the characteristics of HDL

Answer 9

“trash trucks” of lipid metabolism. They collect cholesterol from peripheral tissues and transport it back to the liver. Non- atherogenic

Question 10

chylomicron formation

Answer 10

triglyceride is hydrolyzed to monoacylglycerol and free fatty acids by pancreatic lipase. Lipids transported across intestine wall, re-synthesized into triglycerides and packaged into chylomicron particles containing apoprotein B48

Question 11

chylomicron metabolism pathway

Answer 11

chylomicrons screted into gut lymphatics > enter central circulation > acquire apoproteins C-2 and E from HDL > triglycerides broken down by lipoprotein lipase at endothelial surface of tissues > chylomicron-remnant particles taken up by liver

Question 12

lipoprotein lipase co-factor

Answer 12

apoprotein C-2

Question 13

VLDL metabolism pathway

Answer 13

VLDL is synthesized in liver with apoprotein B100 > secretio from liver > acquires apoprotein C-2 and apolipoprotein E from HDL > metabolized by lipoprotein lipase to form VLDL remnants and LDL.

Question 14

LDL metabolism pathway

Answer 14

LDL still contains apo B100 from VLDL > cleared from blood by LDL receptor, present on many cells but mainly liver > LDL internalized and regulated hepatic cholesterol synthesis and metabolism

Question 15

HDL vs chylomicrons and VLDL

Answer 15

Unlike chylomicrons and VLDL that deliver lipid to peripheral tissues, high density lipoproteins (HDL) functions in part to bring cholesterol (and to a lesser extent triglyceride) from the periphery back to the liver in what has been called “reverse cholesterol transport”.

Question 16

HDL metabolism

Answer 16

HDL synthesized in liver and intestine contains apo-protein apo A1 > circulates in plasma and picks up free cholesterol from tissues via diffusion and ABC-A1 cassette (facilitated transport) > cholesterol in HDL converted to less polar cholesterol ester via lecithin cholesterol acyltransferase (LCAT) ALSO HDL transfers cholesterol esters to VLDL in exchange for triglycerides via cholesterol ester transfer protein > mature HDL taken up by liver

Question 17

Function of ABC-A1

Answer 17

ATP binding cassette (ABC) transporter - transports cholesterol from peripheral tissues to apo A-1, th core apoprotein of HDL.

Question 18

Deficiency in ABC-A1

Answer 18

causes Tangiers disease- unable to remove cholesterol from peripheral tissues leading to low HDL and premature atherosclerosis. Classic finding is orange tonsils due to accumulation of cholesterol in lymphatic tissues

Question 19

Function of LCAT

Answer 19

Lecithin cholesterol acyl transferase catalyses the transfer of fatty acids from the phospholipid lecithin to un-esterified cholesterol, creating a cholesterol ester which is non polar and more tightly bound to HDL particle. This ensures cholesterol doesnt fall off the HDL and is more efficiently transported back to liver.

Question 20

Deficiency of LCAT

Answer 20

Low HDL levels, corneal opacities, renal insufficiency and hemolytic anemia due to the accumulation of un-esterified cholesterol in tissues. Renal failure is main problem. Atherosclerosis not a problem

Question 21

Function of CETP

Answer 21

Cholesterol ester transfer protein (CETP) is a protein that catalyzes the exchange of the non-polar lipids: cholesterol esters (CE) and triglycerides (tg) between lipoprotein particles of different classes. Usually, CE from HDL is exchanged for tg in VLDL.

Question 22

List functions of apo-lipoproteins

Answer 22

structural, enzymatic co factors, ligands for receptors, or unknown fucntion

Question 23

Examples of apo lipoproteins used for structural backbone

Answer 23

apoB48 for chylomicrons, apoB100 for VLDL and LDL, apo A1 for HDL.

Question 24

Examples of apo lipoproteins used as enzymatic cofactors

Answer 24

apoC2 is a co-factor for LPL- hydrolyzes circulating tg

Question 25

Examples of apo lipoproteins used as ligands for receptors

Answer 25

apoB100 is ligand for LDL receptor. Apo E is ligand for remnant receptor

Question 26

Examples of apo lipoproteins with unknown functions

Answer 26

apo(a)

Question 27

significance of apo(a)

Answer 27

apo(a) is linked to apo B on LDL forming lipoprotein (a). Increased levels are linked with premature atherosclerosis, possibly due to the structural similarity of apo(a) with plasminogen