Lipoprotein Biochemistry

Question 1

Lipid transport

Answer 1

. Hydrophobic lipids (cholesterol/esters, TAGs) transported as lipid-protein complexes
. Lipoproteins have outer amphipathic shell of phospholipids, free cholesterol and apo-protein w/ inner core of TAG and cholesterol esters

Question 2

Chylomicrons source, major lipid, and major apolipoprotein

Answer 2

. Intestine
. TAGs through diet
. B-48, C-II, E

Question 3

VLDL source, major lipid, and major apolipoprotein

Answer 3

. Liver
. endogenous TAGs
. B-100, C-11, E

Question 4

LDL source, major lipid, and major apolipoprotein

Answer 4

. VLDL
. Cholesterol, cholesterol esters
. B-100

Question 5

HDL source, major lipids, and major apolipoprotein

Answer 5

. Liver, intestine
. Cholesterol, cholesterol esters
. A-I/II, C-II, E

Question 6

Exogenous pathway for chylomicrons/TAGs/cholesterol metabolism

Answer 6

. Dietary lipid packaged into chylomicrons
. Apo C-II activates extracellular lipoprotein lipase (adipose and muscle)
. TAGs in chylomicrons hydrolyzed to release FAs that are stored or used as energy source
. TAG-poor chylomicron remnants cleared from blood via remnant receptors on surface of liver cells that take apo B-48
. Apo E is removed and degraded

Question 7

Endogenous pathways for lipoprotein metabolism

Answer 7

. Endogenously synthesized TAG and cholesterol packaged into VLDL in liver
. Apo C-II activated lipoprotein lipase for TAG release to FA in VLDL
. VLDL remnants (IDL) undergo remodeling w/ HDL and CETP and are converted to cholesterol-rich LDL particles that only contain B-100 through giving cholesterol for phospholipids in CETP
. LDL delivers cholesterol to organs/tissues by receptor mediated endocytosis via apo B-100 binding to surface LDL receptor

Question 8

HDL

Answer 8

. Transports excess cholesterol from peripheral tissues to liver via reverse cholesterol transport
. Lowers risk of cardiovascular disease

Question 9

Reverse cholesterol transport

Answer 9

. Export cholesterol from cells to HDL via membrane-assoc. transport protein ABCA1
. Cholesterol delivered to newly synthesized lipid-poor HDL
. Cholesterol in HDL esterified by lecithin: cholesterol acyltransferase (LCAT) that is activated by apo-A1 so cholesterol is sequestered to HDL core
. Cholesterol in HDL delivered to liver directly (HDL binding to SR-B1 receptor) OR indirectly (transfer of cholesterol esters to VLDL/LDL via CETP)

Question 10

HDL protein composition

Answer 10

. 48 proteins assoc. with it 
. Cholesterol and lipoprotein metabolism
. Acute-phase-response proteins 
. Regulators of complement activation
. Endopeptidase inhibitors 
. Heparin-binding molecules

Question 11

LDL receptor and regulation

Answer 11

. LDL docks

. Endocytosed and broken down into FA, amino acids, and cholesterol that is then released into the cell

Question 12

What cell has unregulated LDL receptor?

Answer 12

Macrophages, turn into foam cells in pathologic conditions do to uptake of so much LDL

Question 13

Cholesterol drug treatment with PCSK9

Answer 13

. Drug inhibits proteosome that degrades LDL receptors

. LDL receptor is recycled back up into the membrane to inc. amount of receptors and dec. amount of LDL in blood