Lipoprotein Metabolism

Question 1

Apo B-48 Lipoproteins

Answer 1

Chylomicron (dietary lipids)

CM Remnants

Question 2

Apo B-100 Lipoproteins

Answer 2

VLDL (liver synthesized TAGs)

IDL

LDL

Question 3

Apo A-1

Answer 3

HDL

Question 4

Chylomicron

Structural protein
Activator of LPL
Ligand to Apo-E Receptor

Answer 4

Structural: Apo B-48

Activator of LPL: Apo C-II

Ligand to Apo-E Receptor: Apo E

Question 5

CM Remnant

Structural protein
Activator of LPL
Ligand to Apo-E Receptor

Answer 5

Structural: Apo B-48

Activator of LPL: NONE

Ligand to Apo-E Receptor: Apo E

Question 6

VLDL

Structural protein
Activator of LPL
Ligand to Apo-E Receptor

Answer 6

Structural: Apo B-100

Activator of LPL: Apo C-II

Ligand to Apo-E Receptor: Apo E

Question 7

IDL

Structural protein
Activator of LPL
Ligand to Apo-E Receptor

Answer 7

Structural: Apo B-100

Activator of LPL: NONE

Ligand to Apo-E Receptor: Apo E

Question 8

LDL

Structural protein
Activator of LPL
Ligand to Apo-E Receptor

Answer 8

Structural: Apo B-100

Activator of LPL: NONE

Ligand to Apo-E Receptor: NONE

Question 9

HDL

Structural protein
Activator of LPL
Ligand to Apo-E Receptor

Answer 9

Structural: Apo A-I

Activator of LPL: Apo C-II

Ligand to Apo-E Receptor: Apo E

Question 10

Lipoprotein Size Rank

biggest to smallest

Answer 10

CM, VLDL, IDL, LDL, HDL

Question 11

Lipoprotein Density

least to most

Answer 11

CM, VLDL, IDL, LDL, HDL

Question 12

Chylomicron metabolism

Answer 12

1. dietary and apo B-48 in enterocyte synthesized into CM via MTP
2. Nascent CM released to lymphatic system, then to bloodstream
3. CM matures in blood receiving Apo C-II and APO E from circulating HDLs
4. At tissue cells, LPL splits TAGs to glycerol and FA. Glycerol to liver, FA taken up by cells
5. Apo CII is returned to HDL, leaving a CM remnant containing Apo B-48, Apo E and few/no TAGs
6. CM remnant binds to hepatic apo E receptor, taken into liver.
7. free cholesterol, amino acids, vitamins released to cytosol

Question 13

LPL

Answer 13

Lipoprotein Lipase

attached to ECM of endothelial cells in capillaries

Not circulating in blood

Adipose LPL stimulated by insulin (fed)

Skeletal and cardiac LPL stimulated by glucagon/epi (fasting)

Question 14

VLDL, IDL, LDL Metabolism

Answer 14

1. VLDL assembled in liver with Apo B-100, use MTP to package VLDL with lipids
2. In blood, nascent VLDL modified to mature VLDL by receiving Apo C-II and Apo E from HDLs
3. Apo C-II activates LPL, which hydrolyzes TAGs to glycerol (to liver) and FFAs (to tissues)
4. Apo C-II returned to HDL, leaving CE and IDL with B-100, apo E and TAGs
5. 1/2 IDL taken up via hepatic apo E

1/2 digested by hepatic lipase to reduce TAG and donale Apo E to HDL, becoming LDL

6. 2 fates of LDL:
7. bind to LDL receptors on liver (70%)
8. bind to LDL receptors on surface of extra hepatic tissues (30%)
9. Excess LDL in blood means LDL receptors are saturated and LDL available for macrophages. Suggested to be onset of atherosclerosis

Question 15

HDL Metabolism

Answer 15

1. Synthesized in liver or enterocytes w/ low levels of TAGs and CE
2. Receive Apo A-I, Apo C-II and Apo E in liver/enterocyte, appears in blood as small discoidal nascent HDL
3. Nascent HDL encounter tissue cells it fills with CEs and takes a globular, mature shape
4. Reverse cholesterol transport removes cholesterol from loaded cells to be returned to liver for elimination. Requires ABCA1 protein. ABCA1 moves cholesterol from inner to outer leaflet so HDL can accept it.
5. LCAT traps cholesterol in HDL. Activated by Apo A-I and converts cholesterol to CE.
6. CE accumulation transitions HDL to HDL2
7. CETP transfers CE from HDL to VLDL in exchange for TAG. VLDL catabolized to IDL and CE is taken up by liver
8. CE and C uptake in liver moderated by SR-B1 receptor which binds to HDL