Lipid transport

Question 1

HDL

Answer 1

Reverse cholesterol transport (-> elimination)

Liver: -> apoA1 ->
Periphery: ABCA releases chol from cell
LCAT (aka PCAT) loads chol into HDL -> HDL3 -> HDL2

Chol ester transfer protein (CETP):
Transfer esters to VLDL, LDL (exchange for TG, PL)

Receptor = SR-B1 in liver, adrenal cortex

Question 2

Overview of plasma lipoproteins

Answer 2

Neutral core (TG, esters) + amphipathic shell (apo, PL, free chol)
All exchange lipids, proteins, etc

Chylomicrons - large, from intestine, least dense
 - Apo B48
VLDL - released from liver
 - Apo B100
LDL
HDL - reverse transport from periphery

Question 3

Chylomicron metabolism

Answer 3

microsomal TG transfer protein (MTP):
- ER + Apo B48 -> Golgi vesicle
Receives Apo E and CII from HDL
CII stimulates lipoprotein lipase in capillary wall (adipose, muscle) -> FFA -> uptake
- CII recycled to HDL as TG % decreases -> “remnant”
ApoE -> hepatic uptake via endocytosis

Question 4

VLDL metabolism

Answer 4

Secreted by liver = Apo B100 + TG (requires MTP for synthesis)
Get apo CII and E from HDL
CII -> activates LPL -> uptake of FFA

CETP: exchange TG -> HDL, chol ester IDL (-> some uptake via apo E)
-> LDL -> uptake via B100

Question 5

LDL metabolism

Answer 5

Created from VLDL following LPL uptake and CETP exchange
(much less TG, more chol and chol esters)

Endocytosis:
Receptor binds B100 and E (LDL or IDL, chylomic remnants)
-> clathrin pit -> internalized
-> fuse -> low pH -> separation (CURL = compartment for uncoupling of receptor and ligand) -> receptors recycled

Question 6

Regulation of lipoproteins

Answer 6

Hormones:
- insulin -> LPL -> TG uptake as FFA
- thyroid -> LDL binding
Genetics
- receptor alleles -> atherosclerosis, Alzheimers, etc
Statins inhibit HMG CoA reduct -> SREBP -> LDL uptake

Uptake -> cellular cholesterol
(-) HMG CoA reductase
(-) LDL receptor
(+) ACAT -> esterifies chol for storage