Lipids and Lipoprotein

Question 1

Energy storage in fat and muscle

Answer 1

100,000 kCal in TAGs

Question 2

What is the major storage of fatty acids?

Answer 2

Triacylglycerols (TAGs)

Question 3

Sources of TAG

Answer 3

Dietary TAG - processed by intestinal cells

De Novo TAG - in hepatocytes and adipocytes

Question 4

What happens to TAGs in intestinal cells?

Answer 4

Dietary TAGs are broken down into MAG and FFA by pancreatic lipases

Question 5

What is formed from the packaging of TAGs with apolipoprotein and other lipids?

Answer 5

Chylomicrons - which are released into the lymphatic system and enter blood via thoracic duct

Question 6

TAG synthesis in the liver

Answer 6

• Fatty acids synthesize de novo in hepatocytes

- TAG + apolipoproteins + other lipids –> VLDL (released into bloodstream)

Question 7

Steps in TAG synthesis in the liver?

Answer 7

G3P –> lysophosphatidic acid –> phosphatidic acid –> DAG –> TAG

Question 8

What is added to G3P to form TAGs?

Answer 8

FFA synthesized in liver from acetyl CoA

Question 9

What promotes TAG synthesis in hepatocytes?

Answer 9

Excess cardbohydrates

Question 10

What is the backbone for TAG synthesis in adipocytes?

Answer 10

G3P

Question 11

How are TAGs formed in adipocytes?

Answer 11

G3P and FFA (from breakdown of chylomicrons and VLDL in blood) combine to form TAGs

Question 12

What promotes TAG synthesis in adipocytes?

Answer 12

Excess carbohydrates and fats

Question 13

How are fatty acids broken down in mitochondria?

Answer 13

via beta-oxidation

Question 14

4 major lipases for breakdown of TAGs

Answer 14

• hormone sensitive lipase (HSL)
• lipoprotein lipase (LPL)
• monoacylglycerol lipase (MAG Lipase)
• ATGL

Question 15

What modulates activity of HSL?

Answer 15

Phosphorylation

Question 16

2 major signals to promote mobilization of TAGs

Answer 16

Hunger and Excercise

Question 17

What are the major controllers that phosphorylate (and activate HSL?

Answer 17

• glucagon (secreted in response to hunger)

- epinephrine (secreted in response to exercise)

Question 18

What does glucagon and epinephrine promote in HSL?

Answer 18

lipolysis in adipocytes

Question 19

What inhibits mobilization of TAGs?

Answer 19

Fed status signal

• insulin secreted in response to high carb meal
• dephosphorylation of HSL to inhibit lipolysis

Question 20

What do you call a family of proteins that coat lipid droplets in adipocytes and muscle cells?

Answer 20

Perilipin - prevents lipolysis from occurring

Question 21

How does perilipin regulate lipolysis?

Answer 21

By controlling physical access to HSL

Question 22

What is the consequence of overexpression of Perilipin 1?

Answer 22

Inhibits lipolysis

Question 23

What transports TAGs and cholesterol?

Answer 23

Lipoproteins

Question 24

How does lipoproteins contribute to lipid metabolism?

Answer 24

-serve as ligands that bind to internalize lipoproteins and activate various enzymes

Question 25

5 types of lipoproteins

Answer 25

- Chlyomicrons - VLDL - IDL - LDL (bad cholesterol) - HDL (good cholesterol)

Question 26

Which type of lipoprotein has the most TAGs and least protein?

Answer 26

Chylomicrons

Question 27

Which type of lipoprotein has the least TAGs and most protein?

Answer 27

HDL (high protein, and phospholipid content)

Question 28

Beneficial effects of HDL

Answer 28

- HDL levels correlate positively with reduced CAD risk - HDL has the ability to reverse cholesterol transport - HDL-C scavenges and removes LDL from peripheral and transports it to liver where it can be recycled and processed - anti-oxidant and anti-inflammatory properties - increased by weight loss and exercise

Question 29

Type 1 Hyperlipoproteinemia | aka hyperchylomicronemia

Answer 29

- deficiency in apoC-II or defective lipoprotein lipase - inability to hydrolyze TAGs in chilomycrons and VLDL - abd pain, xanthomas, acute pancreatitis - high chylomicrons and high TAGs - treat with low fat diet

Question 30

Type 2a and 2b hyperlipoproteinemia | aka hypercholesterolemia

Answer 30

- LDL receptor is completely (2a) or partially (2b) defective - defect in uptake of LDL (ApoB 100 recognition impaired) - can cause atherosclerosis, xanthomas - high cholesterol, normal TAG (2a), high TAG (2b), high LDL, high VLDL (2b)

Question 31

Type 2 hyperlipoproteinemia cholesterol levels

Answer 31

Normal cholesterol: 130-200 mg/dL Heterozygous: 300-500 mg/dL Homozygous: >800 mg/dL

Question 32

Rate limiting enzyme of cholesterol biosynthesis and the target of statins:

Answer 32

HMG CoA reductase

Question 33

Structure of lipoproteins:

Answer 33

outer shell: monolayer of phospholipids, free cholesterol and apolipoproteins inner core: hydrophobic TAGs, cholesterol esters

Question 34

Apo-lipoproteins on Chylomicron

Answer 34

- ApoB-4: facilitates transport of chylomicron in blood - ApoC-II: activates capillary lipoprotein lipase to accelerate degradation of TAGs - ApoE: acts as a ligand that are taken up by hepatocytes more quickly

Question 35

VLDL Apolipoproteins

Answer 35

- ApoB-100 - ApoC-II - Apo-E

Question 36

IDL Apolipoproteins

Answer 36

- Apo-100 | - ApoE

Question 37

LDL Apolipoproteins

Answer 37

- ApoB-100: uptake into cells | - lots of "bad cholesterol"

Question 38

HDL Apolipoproteins

Answer 38

- smallest, most dense, highest phospholipid and protein content, very little cholesterol - contains ApoA-I, ApoC-II, ApoE

Question 39

Heterozygous type 2 hyperlioproteinemia

Answer 39

-responds to diet, statins and bile acid binding resins

Question 40

Homozygous type 2 hyperlioproteinemia

Answer 40

- need LDL apheresis and liver transplant | - CAD risk and high death rate before teenager years

Question 41

What does the death of foam cell, platelet adhesion, and recruitment of smooth muscle cells leads to?

Answer 41

Development of arterial plaques that lead to atherosclerosis