Lipids and Lipoproteins

Question 1

3 sources of TAGs

Answer 1

Dietary TAG via intestinal cells
De novo TAG in hepatocytes
De novo TAG in adipocytes

Question 2

TAG synthesis in intestinal cells (3 steps)

Answer 2

Dietary TAG is broken down into MAG and FFA in lumen.
Intestinal cells resynthesize TAG.
TAG is packaged into chylomicron and is released into the thoracic duct.

Question 3

TAG synthesis in the liver (3)

Answer 3

Glc and glycerol form G3P using different pathways.
FA CoA is added to G3P to eventually form TAG.
TAG is transported in VLDL in the blood.

Question 4

What is the unique enzyme, found only in the liver, that converts glycerol to G3P?

Answer 4

Glycerol kinase

Question 5

TAG synthesis in the liver is promoted by what?

Answer 5

Excess carbs.

Question 6

TAG synthesis in adipocytes

Answer 6

Glucose forms G3P.
FFA is obtained by the breakdown of chylomicrons and VLDL in the blood via capillary lipoprotien lipase.
Together Glc and FFA form TAGs and are store them in the adipocyte.

Question 7

TAG synthesis in adipocytes is promoted by:

Answer 7

Excess carbs and fats.

Question 8

Regulation of TAG breakdown

Glucagon, epi, NE, Insulin

Answer 8

Glucagon, NE, epi activate HSL to begin the breakdown of TAG.
Insulin inhibits.
Insulin is released in the fed state. Why would we want to increase fuel in the blood when we are fed?

Question 9

HSL, LPL, MAG lipase

Answer 9

HSL - TAG to DAG
LPL - DAG to MAG
MAG lipase - MAG to glycerol
These enzymes, along with ATGL, may have affinity for more than one substrate.

Question 10

Perilipin

Answer 10

Protein that coats lipids droplets in adipocytes and muscle.

Regulate lipolysis by controlling access to HSL.

Question 11

Why is perilipin a target for obesity?

Answer 11

If perilipin is inhibited, TAGs are much mobilized much easier and can be accessed by its enzymes for breakdown.

Question 12

Outer and inner shell of lipoproteins

Answer 12

Outer: phospholipids, free cholesterol, apolipoproteins.
Inner: packed with TAGs and cholesterol.

Question 13

5 basic types of lipoproteins

Answer 13

Chylomicrons
VLDL
IDL
LDL
HDL

Largest to smallest, and increasing levels of TAGs, decreasing levels of protein.

Question 14

Apolipoproteins on chylomicrons (3)

Answer 14

ApoB - 48: facilitates transport.
ApoC - II: activates lipoprotein lipase.
ApoE: facilitates uptake into the liver.

Question 15

Apolipoproteins of VLDL (3)

Answer 15

ApoB - 100
ApoC - 11
ApoE

Question 16

Apolipoproteins of IDL (2)

Answer 16

ApoB - 100

ApoE

Question 17

Apolipoprotein of LDL (1)

Answer 17

ApoB - 100

Question 18

ApoB - 100 function

Answer 18

Facilitates uptake into cells

Question 19

Apolipoproteins of HDL (3)

Answer 19

ApoA - I
ApoC - II
ApoE

Question 20

Chylomicron processing

Answer 20

Chylomicrons are assembled in GI and transported into the lymph.
CLPL hydrolyzes TAGs into glycerol and FFA. ApoC-II is released back to HDL.
Chylomicron is endocytosed by the hepatcoytes via the ApoE receptor.

Question 21

VLDL, IDL, and LDL processing

Answer 21

Assembled in the bloodstream.
CLPL hydrolyzes TAGs into FFA and glycerol. ApoC-II is released back to HDL. Now it is IDL.

IDL loses more TAGs and ApoE to become LDL.
LDL’s ApoB-100 binds to its receptor on target tissue.

Question 22

Atherosclerosis

Answer 22

Defect in the ApoB-100 receptor and LDL remains in the blood.

Question 23

HDL processing

Answer 23

HDL begins as a disk, but as it picks up cholesterol from tissues it becomes spherical. It begins to deliver its apolipoproteins to other lipoproteins in exchange for TAGs
Eventually, it delivers its load to the liver.

Question 24

Why is HDL good cholesterol?

Answer 24

Scavenges and removes LDL from periphery and transports it to the liver. Is also believed to have an antioxidant effect/anti-inflammatory effect.

Question 25

Type I hyperlipoproteinemia

Answer 25

Inability to hydrolyze TAGs in chylomicrons and VLDL.
Due to a deficienct in CLPL or ApoC-II.
May present in infancy.
Plasma TAG level > 1000 md/dl.
Major clinical symptom is xanthoma (nodules of lipids around the eyes).

Question 26

Type II hyperlipoprotienemia

Answer 26

Defect in LDL receptor (cannot participate in receptor-mediated endocytosis) - cannot recognize ApoB-100.
Can cause atherosclerosis.
Untreated homozygous individuals die of CAD very early. Heterozygous develop CAD by age 40.
Patients will need to change their diet, or possibly a liver transplant if severe.