Lecture 2

Question 1

Apo B-48

Answer 1

Unique to chylomicrons
Carries dietary TAG, cholesterol, fat soluble vitamins, and cholesterol esters to peripheral tissues.
Made in the intestinal mucosal cells
Truncated form of Apo B100

Question 2

Chylomicron metabolism Steps

Answer 2

1. ) Nascent Chylomicrons are released into the lympahtic circulation and then the blood.
2. )Apo E and Apo C are added to the nascent chylomicron in the blood.
3. )LPL on the capillary walls is activated by Apc C-II to hydrolyze TAG
4. ) Paritcle decreased in size and increases in density
5. ) Apo C is returned to the HDL creating a chylomicron remnant.
6. ) Remnant is taking up by the liver through recognition of Apo E

Question 3

Lipoprotein Lipase Structure

Answer 3

LPL is an antiparallel Homodimer
N terminal domain- Lypolytic site
C teminal domain- binds to the lipoprotein ( Apo C-11) and gives substrate specificity

Question 4

Patients with deficiency of LPL or ApoC-II

Answer 4

accumulate cylomicron TAG in the plamsa and are at higher risk for panceatitis

Question 5

VLDL

Answer 5

very low density lipoproteins
produced by the liver
contain Apo B-100
functions to ccarry lipids from the liver to pheripheral tissues.

Question 6

VLDL Metabolism Steps

Answer 6

1. )nascent VLDL is secreted into the bloodstream by the liver.
2. )Apo E and Apo C are added from HDL . Some TAGs are exchanged for cholesterol esters from HDLs, in a reaction catalyzed by cholesterol ester exchange protein (CETP)
3. )LPL on the capillary walls is activated by Apc C-II to hydrolyze TAG
4. ) VLDL is converted to LDL in the blood stream, adn Apo C and APo E are returned to HDLs
5. ) LDL particle binds to a receptor on hepatocytes and extra hepatic tissue.

Question 7

hepatic steatosis

Answer 7

(Nonalcoholic Fatty liver)

caused by an imbalance of TAG synthesis and VLDL secretion

Question 8

familial Type III hyperlipoproteinemia

Answer 8

Apo E-2 binds poorly to receptors.

They also have hypercholesterolemia and premature athlerosclerosis.

Question 9

Apo E4 significance

Answer 9

confers increased susceptibility and decreased age of onset of alzheimer’s disease.

Question 10

CETP

Answer 10

Cholesterol ester transfer protein
Exchanges TAGs from VLDLs for Cholesterol esters from HDL.
Driven by increased concentration of TAGs
(explains why increased TAG in the blood results in increased cholesterol return to the liver via VLDLs and IDL particles)

Question 11

ACAT

Answer 11

Acyl CoA cholesterol acyltransferase

Cholesterol to Cholesterol ester (form that can be stored in cells when cholesterol is not immediately needed)

Question 12

LDL Metabolism Steps

Answer 12

1.) ApoB 100 binds
2.) complexed endocytosed in clathrin coated pits
3.) fusion with over vesicles forms endosomes
4.)pH of endosome drops through action of ATP dependant proton pump, in order to seperate the LDL from the LDL receptor
5.) A.) receptor is recycled to the membrane
B.) lysosomal hydrolases degrade LDL

Question 13

LDL

Answer 13

functions to provide cholesterol to the peripheral tissues and return it to the liver.
contains less TAG than VLDL and more cholesterol and cholesterol esters

Question 14

familial Type II hyperlipoproteinemia

Answer 14

deficiency in LDL receptor, or Apo B-100 (autosomal recessive)

(autosomal dominant form has increased activity of a protease that degrades the LDL receptor)

Question 15

oversupply of cholesterol can diminish expression of

Answer 15

Liver LDL receptor and HGM CoA reductase (first step in cholesterol biosysthesis)

Question 16

LDL receptor domains

Answer 16

1.) LDL binding region (decreased pH causes the Ca from this region to be released causing a conformation change in region 2)
2.) EGF-like and transducin beta subunit-like domain
(where conformational change occurs in response to acidic pH)
3.) N-linked oligosaccaride region
4.) O-linked oligosaccaride region (3&4 extent LDL binding region away from membrane surface)
5.) alpha-helical pass
6.) Cytosolic domain that associates with clathrin coated pits

Question 17

Tangier Disease

Answer 17

Deficiency of ABCA1 (which catalyzes efflux of cholesterol from pheripheral tissues)
lead to absence of HDL particals because free ApoA-1 gets degraded

Question 18

LCAT

Answer 18

lecithin cholesterol acyl transferase
activated by Apo A-1
esterifies choleserol taken up by HDLs (this maintains the cholesterol gradient so HDLs can continue taking up more cholesterol)

Question 19

HDL

Answer 19

formed in blood by addition of lipids to ApoA-I (which is synthesized in the liver and intestines)
circulating supplier of Apo E and Apo C
Takes up cholesterol from peripheral tissues and return it to the liver as cholesterol esters

Question 20

SR-B1

Answer 20

scavenger receptor

binds HDL and allows the liver to take up Cholesterol esters from the HDL

Question 21

SR-A

Answer 21

Allows macrophages to endocytise LDLs that have undergone oxidative damage, when this happens macrophages turn into foam cells which participate in plaque formation.

Question 22

Athleroslerotic plaques and thrombus formation

Answer 22

1. ) A cap forms over the plaque obstruction the blood vessel
2. ) vascular smooth muscle cells migrate from the tunica media and secrete plaque matrix material and metaloproeases that thin the fibrous cap.
3. ) cap eventually ruptures exposing cap contents to procoagulants within the circulation.