Lipoprotein Lecture (Lecture 3)

Question 1

Exogenous pathway involves …

Answer 1

chylomicrons

Question 2

Endogenous pathway involves …

Answer 2

mainly low density lipoproteins

Question 3

Reverse transport involves …

Answer 3

HDL

Question 4

Food with dietary cholesterol?

Answer 4

animals only

Question 5

What happens to dietary cholesteryl esters in the lumen?

Answer 5

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

Question 6

Where in the GI tract are sterols absorbed?

Answer 6

Epithelial cells of the jejunum take up sterols from the lumen of the intestine rather indiscriinately via binding to NPC1L1, followed by endocytosis

Question 7

What is NPC1L1?

Answer 7

An abbreviation of Niemann-Pick C1-like protein 1. Found on the gastrointestinal tract epithelial cells; critical mediator of sterols absorption.

Question 8

Describe the absorption of cholesterol

Answer 8

The intestine incorporates cholesterol and cholesteryl esters into chylomicrons, and after loss of associated triglycerides, the cholesterol-rich chylomicron remnants enter the liver

Question 9

Apolipoprotein C-II?

Answer 9

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)

Question 10

Apolipoprotein CIII?

Answer 10

lipoprotein lipase inhibitor

Question 11

Apolipoprotein E?

Answer 11

(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) **

Question 12

Explain the receptor-mediated clearance by the liver by binding to apolipoprotein E?

Answer 12

Apolipoprotein E on chylomicron remnants binds to the LDL receptor-related protein 1 (LRP1) on hepatocytes, and the remnants enter via endocytosis

Question 13

What is the function of lipoprotein lipase?

Answer 13

cleaves fatty acids from the triacylglycerols present in the anhydrous core in lipoproteins, thereby diminishing the TAG content of the lipoprotein

Question 14

What do triacylglycerides degrade into (i.e. the effect of lipases)?

Answer 14

FFAs + glycerols; lipases hydrolyze triglycerides inside chylomicrons or VLDL to fatty acids and glycerol

Question 15

Two lipases

Answer 15

(1) lipoprotein lipase

(2) hepatic lipase

Question 16

Where are the lipases located?

Answer 16

lipoprotein lipase: on the walls of blood capillaries of tissues
hepatic lipase: in capillaries of the liver

Question 17

Why are lipases located on capillaries?

Answer 17

Allows free fatty acids to return to circulation

Question 18

How does lipoprotein lipase work?

Answer 18

(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)

Question 19

Where do the fatty acids go?

Answer 19

80% of the fatty acids are taken by adipose tissue, heart and muscle and 20% are returned back to the liver.

Question 20

Uses of fatty acids?

Answer 20

(1) storage (by adipose cells)
(2) used for energy (by muscles)
(3) transported by serum albumin until uptake occurs

Question 21

Hepatic Lipase

Answer 21

(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

Question 22

Where are chylomicrons synthesized?

Answer 22

small intestine

Question 23

Purpose of chylomicrons?

Answer 23

transport dietary lipids; dietary TAGs are delivered to adipose and ther peripheral tissues

Question 24

Characteristics of chylomicrons?

Answer 24

98% lipid, large sized, lowest density

Question 25

Apolipoproteions on chylomicrons?

Answer 25

Apo B-48 (provides an indicator of intestinal derived lipoproteins in circulation), Apo C-II, Apo-CIII, and Apo E

Question 26

Fasting blood sample and concentration of chylomicrons

Answer 26

a fasting blood sample is taken in order to not affect the results by the present of “contaminating” chylomicrons. Will clear from the blood within a few hours of a meal (i.e. half-life for a given particle is expressed in terms of minutes)

Question 27

What does dietary cholesterol inhibit?

Answer 27

Dietary cholesterol inhibits cholesterol synthesis by the liver

Question 28

What apoliprotein and lipids are contain in nascent chylomicron?

Answer 28

Apoprotein B48 and a large cargo of triacylglycerol (with a little cholesterol, cholesterol ester and phospholipid)

Question 29

What apolipoprotein do chylomicrons receive from HDL?

Answer 29

Apoproteins E and CII

Question 30

How do chylomicrons becomme chylomicron remnants?

Answer 30

As triacylglycerol is lost; TAGs are lost because lipoprotein lipase hydroxylses TAGs to liberate free fatty acids which diffuse into the local tissues

Question 31

Role of the chylomicron remnant?

Answer 31

(1) dissociate fro LPL
(2) return apoprotein CII to HDL
(3) taken up by the liver (liver recognizes B48 and E)