lecture 8: lipoproteins and cholesterol transport

Question 1

lipoproteins

Answer 1

carry chylomicrons (small intestine) or VLDLs (liver)

Question 2

loss of TAG from the core of lipoproteins

Answer 2

VLDLs become IDL and LDL

Question 3

apo A1

Answer 3

found only in HDL
flexible and weakly associated with HDL surface
promotes desorption of free cholesterol from cell membranes
activates LCAT (produced cholesterol esters)

Question 4

Apo B

Answer 4

found in chylomicrons, VLDL, IDL, LDL

Apo B100 produced in liver, promotes endocytosis

Apo B48: made in intestinal cells, cannot initiate endocytosis

Question 5

LPL in adipose tissue

Answer 5

fasting state: downregulated
fed: upregulated
high Km (smaller affinity, never saturated)

Question 6

LDL receptor

Answer 6

role in cholesterol uptake

binds lipoproteins at clathrin coated pits
clathrin coat removed via endocytosis and LDLRs are sent back to plasma membrane

Question 6

LDL in heart/muscle tissue

Answer 6

fasting state: levels maintained
lower Km /higher affinity
saturated at low concentrations (rate dependent on enzyme)

Question 7

key event in atherogenesis

Answer 7

retention of apo B-containing lipoproteins in the intima of arterial walls

Question 8

atherogenesis

Answer 8

smaller apo B containing lipoproteins (LDL) move across arterial walls to transport cholesterol
LDL susceptible to modifications at branch-points > modified LDLs prone to aggregate > activated monocytes have inflammatory response, macrophages oxidize LDLs and become lipid-filled foam cells

Question 9

synthesis of chylomicrons

Answer 9

TAG-poor monolayer of phospholipids encapsulate cholesteryl esters
TAG transferred
fuses with apoB48 containing particle
translocated to golgi

Question 10

synthesis of VLDL

Answer 10

phospholipid shell with apoB100
TAG added

Question 11

LPL (lipoprotein lipase)

Answer 11

hydrolyzes surface TAG

Question 12

apo C2

Answer 12

activates LPL

Question 13

ACAT

Answer 13

esterifies free cholesterol

Question 14

cholesterol transport by HDL

Answer 14

brings excess cholesterol back to liver > bile acids > excreted

Question 15

how does liver convert HDL for excretion?

Answer 15

a-HDL comes to liver
SR-B1: liver removes cholesteryl esters
Pre-B HDL: lipid poor transporting away from liver, can cross capillary endothelium
ACBA1 transfers phospholipids and free cholesterol to Pre-B-HDL > disk shape > re-enters plasma > reformation of a-HDL