Lesson 20

Lesson 20. Cholesterol and Lipoproteins II - Offner 1. What is true about the origin, content, features, function, mechanism, and details about chylomicrons? a. Intestine; Dietary lipids; TAG-rich ApoB-48CE, deliver exogenous TAG to cell, TAG hydrolyzed by LPL/ApoC, Convesion to chylomicron remnant C-II transferred to HDL, Uptake by liver, Remnant receptor activated by apo-E b. Liver; Liver-made lipids, TAG-rich ApoB-100CE, delivery endogenous TAG to cell; TAG hydroxide by LPL/ApoCII, Conversion to remnant IDL C-II transferred to HDL further conversion to LDL or uptake by liver with LDL receptor and ApoE c. IDL catabolism; CE-rich;one Apo-B100 only; deliver cholesterol to cell; Uptake LDL receptor Apo-B100; destruction in liver d. Liver/intestine/catabolism; Protein-rich; ApoACE, reverse cholesterol transport to live + ApoCE reservoir; cholesterol esterified by LCAT; activated by apoA; apoCE exchanged to VLDL and LDL by CETP for TAGs; Uptake by liver via apoA 1. A: Chylomicrons: Intestine; Dietary lipids; TAG-rich ApoB-48CE, deliver exogenous TAG to cell, TAG hydrolyzed by LPL/ApoC, Convesion to chylomicron remnant C-II transferred to HDL, Uptake by liver, Remnant receptor activated by apo-E 2. What is true origin, content, features, function, mechanism, and details about very low density lipoproteins (VLDL)? a. Intestine; Dietary lipids; TAG-rich ApoB-48CE, deliver exogenous TAG to cell, TAG hydrolyzed by LPL/ApoC, Convesion to chylomicron remnant C-II transferred to HDL, Uptake by liver, Remnant receptor activated by apo-E b. Liver; Liver-made lipids, TAG-rich ApoB-100CE, delivery endogenous TAG to cell; TAG hydroxide by LPL/ApoCII, Conversion to remnant IDL C-II transferred to HDL further conversion to LDL or uptake by liver with LDL receptor and ApoE c. IDL catabolism; CE-rich;one Apo-B100 only; deliver cholesterol to cell; Uptake LDL receptor Apo-B100; destruction in liver d. Liver/intestine/catabolism; Protein-rich; ApoACE, reverse cholesterol transport to live + ApoCE reservoir; cholesterol esterified by LCAT; activated by apoA; apoCE exchanged to VLDL and LDL by CETP for TAGs; Uptake by liver via apoA 2. B: Liver; Liver-made lipids, TAG-rich ApoB-100CE, delivery endogenous TAG to cell; TAG hydroxide by LPL/ApoCII, Conversion to remnant IDL C-II transferred to HDL further conversion to LDL or uptake by liver with LDL receptor and ApoE

3. What is true origin, content, features, function, mechanism, and details about low density lipoproteins (LDL)? a. Intestine; Dietary lipids; TAG-rich ApoB-48CE, deliver exogenous TAG to cell, TAG hydrolyzed by LPL/ApoC, Convesion to chylomicron remnant C-II transferred to HDL, Uptake by liver, Remnant receptor activated by apo-E b. Liver; Liver-made lipids, TAG-rich ApoB-100CE, delivery endogenous TAG to cell; TAG hydroxide by LPL/ApoCII, Conversion to remnant IDL C-II transferred to HDL further conversion to LDL or uptake by liver with LDL receptor and ApoE c. IDL catabolism; CE-rich;one Apo-B100 only; deliver cholesterol to cell; Uptake LDL receptor Apo-B100; destruction in liver d. Liver/intestine/catabolism; Protein-rich; ApoACE, reverse cholesterol transport to live + ApoCE reservoir; cholesterol esterified by LCAT; activated by apoA; apoCE exchanged to VLDL and LDL by CETP for TAGs; Uptake by liver via apoA 3. C: LDL: IDL catabolism; CE-rich;one Apo-B100 only; deliver cholesterol to cell; Uptake LDL receptor Apo-B100; destruction in liver

4. What is true origin, content, features, function, mechanism, and details about high density lipoproteins (HDL)? a. Intestine; Dietary lipids; TAG-rich ApoB-48CE, deliver exogenous TAG to cell, TAG hydrolyzed by LPL/ApoC, Convesion to chylomicron remnant C-II transferred to HDL, Uptake by liver, Remnant receptor activated by apo-E b. Liver; Liver-made lipids, TAG-rich ApoB-100CE, delivery endogenous TAG to cell; TAG hydroxide by LPL/ApoCII, Conversion to remnant IDL C-II transferred to HDL further conversion to LDL or uptake by liver with LDL receptor and ApoE c. IDL catabolism; CE-rich;one Apo-B100 only; deliver cholesterol to cell; Uptake LDL receptor Apo-B100; destruction in liver d. Liver/intestine/catabolism; Protein-rich; ApoACE, reverse cholesterol transport to live + ApoCE reservoir; cholesterol esterified by LCAT; activated by apoA; apoCE exchanged to VLDL and LDL by CETP for TAGs; Uptake by liver via apoA 4. D: Liver/intestine/catabolism; Protein-rich; ApoACE, reverse cholesterol transport to live + ApoCE reservoir; cholesterol esterified by LCAT; activated by apoA; apoCE exchanged to VLDL and LDL by CETP for TAGs; Uptake by liver via apoA 5. What is true about chylomicrons? a. Found in chyle made in intestine b. Transport dietary lipid (TAG) and take up CE from HDL c. Released from intestinal cells by secretory vacuole d. All of the above 5. D: All are true.

6. What is not true about VLDL? a. Made in liver and take up CE from HDL b. Transported into space of Disse then hepatic sinusoids c. ApoB is essential (abetalipoproteinemia) leads to lack of synthesize of VLDL & Chylomicrons d. Both VLDL and chylomicrons are acted on by lipoprotein lipase e. All are true 6. D: All are true 7. Lipoprotein lipase sits on the endothelial capillary cells anchored by proteoglycan chains of heparan sulfate. What is specific to endogenous LPL activity?

I. Phospholipid and apoC-II II. TAG which gets degraded into FA + Glycerol (enter parenchymal cells) III. Induced post-heparin lipolytic activity IV. Variable hormone regulation and enzyme Km in different tissues (Saturated longer, i.e. mammary gland) V. Remnant made after most of TAG is lost and apoC-II leaves a. I, II, III b. I, II, III, IV, V c. I, II, III, V d. I, II, IV, V 7. D: Heparin injection is used to test for post-heparin lipolytic activity 8. How are chylomicrons and VLDL taken up? a. Chylomicron remnant receptor apoE; IDL or LDL apoE/B100/LDL receptor b. Chylomicron remnant receptor apoB48; IDL or LDL apoE/B100/LDL receptor c. Chylomicron remnant receptor apoE; IDL apoE/B100/LDL receptor d. Chylomicron remnant receptor apoE; LDL apoE/B100/LDL receptor 8. A: Chylomicron remnant receptor apoE; IDL or LDL apoE/B100/LDL receptor 9. Which lipoprotein has the most cholesterol? a. VLDL b. HDL c. Chylomicron d. LDL 9. D: LDL: 2/3 of total plasma cholesterol in LDL (40% cholesterylesters; single apoB100;delivers cholesterol to other tissues).

10. What lipoproteins participate in the exogenous and endogenous pathway? a. Exogenous: VLDL, IDL, LDL Endogenous: Chylomicrons Both: HDL b. Exogenous: Chylomicrons Endogenous: VLDL, IDL, LDL Both: HDL c. Exogenous: VLDL, IDL, LDL, HDL Endogenous: Chylomicrons d. None are true

10. B: Chylomicrons operate in the exogenous pathway, whereas VLDL, IDL, and LDL particles operate in the endogenous pathway. HDL particles participate in both pathways.

11. What are the correct order of steps for the receptor-mediated endocytosis of LDL (LDL Pathway)?

I. LDL receptor complex invaginate and forms an endosome pH 5.0 so LDL dissociates from receptor II. Receptor is recycles to membrane and LDL fuses with lysosome to by degraded by lysosomal lipase III. Free cholesterol leaves to 1) Increase ACAT 2) Decrease LDL receptors 3) Suppress HMGCoA reductase IV.Apo B-100 on LDL binds LDL receptor a. IV, I, II, III b. I, II, III, IV c. IV, II, III, I d. I, III, II, IV 11. A: LDL ApoB100 -> Endosome einvag -> Lysomsomal lipase -> ACAT+, LDLRHMGCoARed12. FH is an autosomonal dominate gene dosing disease where cholesterol diet cannot regulate cholesterol biosynthesis. There has cholesterol deposits, high plasma LDL, and risk of atherosclerosis. What did the Goldstein experiments on human fibroblasts show about the FH cells? a. Cholesterol biosynthesis was not suppressed when LDL was added b. Cholesterol biosynthesis was suppressed with LDL was added c. There were higher levels of HMGCoA reductase when LDL is absent d. There were lower levels of HMG CoA reductase when LDL is present 12. A: Cholesterol biosynthesis was not suppressed when LDL was added so HMG CoA levels did not vary.

13. HDL are high in protein, use ApoA, and removes cholesterol from peripheral cells. HDL is made by discs that: a. Are made in intestine b. Are substrates for lecithin-cholesterol acyltransferase (LCAT) which makes unsaturated cholesteryl ester and requires ApoA c. Formed from degradation of chylomicrons or made by liver d. b & c 13. b & c are true. They are great acceptors of cholesterol and discs are a procures of HDL. HDL is made in intestine and liver but not the discs. HDL acts as storage for ApoCE for chylomicrons and VLDL. HDL is discoid in shape and has free cholesterols. LCAT converts HDL into a sphere by increasing chlesterylester. A cholesterol ester transfer protein allows cholesteryl ester of HDL to become part of IDL or chylomicron remnants.

14. What is not true? a. Transfer of CE from HDL to other lipoprotein b. CETP transfers CE to other lipoprotein c. If CETP is blocked HDL increased d. Plasma CE is derived from VLDL 14. D is not true. Plasma CE is derived from LCAT that converts nascent HDL. 15. Plasma HDL acts as a fibroblast free cholesterol acceptor which draws it in via ATP-binding cassette (ABC) using apoA1 and apoE. LCAT esertifies it using ___________ to make ________. This allows cholesterol to move in and stuff HDL. CETP then will transfer some esters to IDL or LDL. Cholesterol esters in LDL contain cholesterol previously on fibroblasts and then returns it to them or the liver. a. Phosphatidylcholine acyl; cholesterol linoleate b. Phosphatidylcholine acyl; cholesterol ester c. cholesterol linoleate;phosphatidylcholine acyl d. cholesterol ester;Phosphatidylcholine acyl 15. A: Cholesterol linoleate is the predominant cholesteryl ester made, since the acyl group in the C2 position of phosphatidylcholine is used by LCAT. 16. Atherosclerosis is correlated to high LDL and low HDL (LDL/HDL ratio above 3.5). It typically occurs in med/large arteries due to accumulation of cholesterylesters + smooth muscle cells.

What is the correct order for atherosclerosis?

I. Injury to arterial endothelium II.Oxidized LDL activate endothelial secretion to draw in monocytes III.Stuffed macrophages become foam cells that stimulate smooth muscle migration from media to intimate IV.Foam cells merge into fatty streaks V. Lipid-laden cells accumulate under intimate to make a fibro-fatty plaque Rupture of plaque leads to partial occlusion VI. Endothelium issues draws in LDL particles to enter intima and get oxidized by free radicals VII. Monocytes convert to macrophages and remove oxidized LDL using scavenger receptors VIII.Foam cells and smooth muscle cells keep removing oxidized LDL IX.Smooth muscles form a fibrous cap over steaks and secrete collagen to stabilize a. I, VI, II, VII, III, VIII, IV, IX, V b. I, II, III, IV, V, VI, VII, VIII, IX, c. I, II, III, IV, V, VI, VII, IX, VIII d. I, VI, II, VII, III, VIII, IV, V, IX

16. A: I. Injury to arterial endothelium VI. Endothelium issues draws in LDL particles to enter intima and get oxidized by free radicals II.Oxidized LDL activate endothelial secretion to draw in monocytes VII. Monocytes convert to macrophages and remove oxidized LDL using scavenger receptors III.Stuffed macrophages become foam cells that stimulate smooth muscle migration from media to intimate VIII.Foam cells and smooth muscle cells keep removing oxidized LDL IV.Foam cells merge into fatty streaks IX.Smooth muscles form a fibrous cap over steaks and secrete collagen to stabilize V. Lipid-laden cells accumulate under intimate to make a fibro-fatty plaque Rupture of plaque leads to partial occlusion 17. How can LDL’s role in atherosclerosis be controlled? a. Discourage LDL accumulation with statins or bile resins b. Discourage oxidation of LDL c. Disrupt inflammatory cycle with anti-oxidant or HDL-boosters d. All of the above 17. D: All of the above