Lipids and Lipoprotein Flashcards
Energy storage in fat and muscle
100,000 kCal in TAGs
What is the major storage of fatty acids?
Triacylglycerols (TAGs)
Sources of TAG
Dietary TAG - processed by intestinal cells
De Novo TAG - in hepatocytes and adipocytes
What happens to TAGs in intestinal cells?
Dietary TAGs are broken down into MAG and FFA by pancreatic lipases
What is formed from the packaging of TAGs with apolipoprotein and other lipids?
Chylomicrons - which are released into the lymphatic system and enter blood via thoracic duct
TAG synthesis in the liver
- Fatty acids synthesize de novo in hepatocytes
- TAG + apolipoproteins + other lipids –> VLDL (released into bloodstream)
Steps in TAG synthesis in the liver?
G3P –> lysophosphatidic acid –> phosphatidic acid –> DAG –> TAG
What is added to G3P to form TAGs?
FFA synthesized in liver from acetyl CoA
What promotes TAG synthesis in hepatocytes?
Excess cardbohydrates
What is the backbone for TAG synthesis in adipocytes?
G3P
How are TAGs formed in adipocytes?
G3P and FFA (from breakdown of chylomicrons and VLDL in blood) combine to form TAGs
What promotes TAG synthesis in adipocytes?
Excess carbohydrates and fats
How are fatty acids broken down in mitochondria?
via beta-oxidation
4 major lipases for breakdown of TAGs
- hormone sensitive lipase (HSL)
- lipoprotein lipase (LPL)
- monoacylglycerol lipase (MAG Lipase)
- ATGL
What modulates activity of HSL?
Phosphorylation
2 major signals to promote mobilization of TAGs
Hunger and Excercise
What are the major controllers that phosphorylate (and activate HSL?
- glucagon (secreted in response to hunger)
- epinephrine (secreted in response to exercise)
What does glucagon and epinephrine promote in HSL?
lipolysis in adipocytes
What inhibits mobilization of TAGs?
Fed status signal
- insulin secreted in response to high carb meal
- dephosphorylation of HSL to inhibit lipolysis
What do you call a family of proteins that coat lipid droplets in adipocytes and muscle cells?
Perilipin - prevents lipolysis from occurring
How does perilipin regulate lipolysis?
By controlling physical access to HSL
What is the consequence of overexpression of Perilipin 1?
Inhibits lipolysis
What transports TAGs and cholesterol?
Lipoproteins
How does lipoproteins contribute to lipid metabolism?
-serve as ligands that bind to internalize lipoproteins and activate various enzymes
5 types of lipoproteins
- Chlyomicrons
- VLDL
- IDL
- LDL (bad cholesterol)
- HDL (good cholesterol)
Which type of lipoprotein has the most TAGs and least protein?
Chylomicrons
Which type of lipoprotein has the least TAGs and most protein?
HDL (high protein, and phospholipid content)
Beneficial effects of HDL
- 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
Type 1 Hyperlipoproteinemia
aka hyperchylomicronemia
- 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
Type 2a and 2b hyperlipoproteinemia
aka hypercholesterolemia
- 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)
Type 2 hyperlipoproteinemia cholesterol levels
Normal cholesterol: 130-200 mg/dL
Heterozygous: 300-500 mg/dL
Homozygous: >800 mg/dL
Rate limiting enzyme of cholesterol biosynthesis and the target of statins:
HMG CoA reductase
Structure of lipoproteins:
outer shell: monolayer of phospholipids, free cholesterol and apolipoproteins
inner core: hydrophobic TAGs, cholesterol esters
Apo-lipoproteins on Chylomicron
- 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
VLDL Apolipoproteins
- ApoB-100
- ApoC-II
- Apo-E
IDL Apolipoproteins
- Apo-100
- ApoE
LDL Apolipoproteins
- ApoB-100: uptake into cells
- lots of “bad cholesterol”
HDL Apolipoproteins
- smallest, most dense, highest phospholipid and protein content, very little cholesterol
- contains ApoA-I, ApoC-II, ApoE
Heterozygous type 2 hyperlioproteinemia
-responds to diet, statins and bile acid binding resins
Homozygous type 2 hyperlioproteinemia
- need LDL apheresis and liver transplant
- CAD risk and high death rate before teenager years
What does the death of foam cell, platelet adhesion, and recruitment of smooth muscle cells leads to?
Development of arterial plaques that lead to atherosclerosis
