Metabolism Lecture 9? - TAG Degradation , Fatty Acid Oxidation, And Ketone Bodies Flashcards
What are two ways that TAG’s are transported?
- Chylomicrons
2. VLDL
State the following for CHYLOMICRONS:
- Main Lipid
- Apoproteins
- Function
- Where is it formed?
- Main Lipid - TAG
- Apoproteins - APO B -48 (A-C)
- Function - transports ietary TAG to adipose and other tissues
- Formed in the intestines
State the following for CHYLOMICRON REMNANTS:
- Main Lipid
- Apoproteins
- Function
- Main Lipid - TAG
- Apoproteins - B-48 ( A-C)
- Function - Delivers dietary tag to the liver
- exchanges TAG for CE from HDL
- delivers CE to the liver
State the following for VLDL:
- Main Lipid
- Apoproteins
- Function
- Where is it formed?
- Main Lipid - TAG
- Apoproteins - B-100
- Function - transports ENDOGENOUSLY SYNTHESIZED TAG to adipose tissue & skeletal & heart muscle
- exchanges TAG for CE from HDL - Where is it formed?
- in the LIVER
State the following for IDL - VLDL remnant:
- Main Lipid
- Apoproteins
- Function
- Where is it formed?
- Main Lipid - TAG & cholesterol
- Apoproteins - B-100, E
- Function - delivers remaining TAG and cholesterol to the liver
- Where is it formed - formed via processing of VLDL in the CIRCULATION
State the following for LDL:
- Main Lipid
- Apoproteins
- Function
- Where is it formed?
- Main Lipid - CHOLESTEROL
- Apoproteins - APO B - 100
- Function - delivers cholesterol to the liver an other cells (steroidogenic cells)
- Where is it formed - via processing of IDL in the CIRCULATION
State the following for HDL:
- Main Lipid
- Apoproteins
- Function
- Where is it formed?
- Main Lipid - CHOLESTEROL
- Apoproteins - APO A’s (C-E)
- Function - accepts cholesterol from peripheral cells and esterifies it and TRANSPORTS CHOLESTEROL ESTERS TO THE LIVER
- Where is it formed - formed in the liver, some formed in the intestines
What is the function of the following:
- APO- CII
- APO - AI
Apo-CII: activates lipoprotein lipase
Apo-AI: activates of lecithin:cholesterol acyltransferase (LCAT)
What is the function of the following:
- APO- CII
- APO - AI
- Apo E
Apo-CII: activates lipoprotein lipase
Apo-AI: activates of lecithin:cholesterol acyltransferase (LCAT)
Apo E : clearance via binding to LRP
What are the structural proteins of the following:
- Chylomicrons
- VLDL and LDL
- HDL
Structural Proteins of Lipoproteins
B-48: Chylomicrons
B-100: VLDL and LDL
A-1: HDL
What activates LCAT?
Apo A-1 binding with HDL
What apoprotein activates LCAT?
What apoprotein activates Lipoprotein Lipase?
Apo A-1 binding with HDL
- Apo C- II
Describe the 6 steps of chylomicron metabolism
- Chylomicrons transport dietary TA and cholesterol
- Nascent chylomicrons are synthesized in th intestines along with Apo - A-1 and APo B-48
- Chylomicrons transiently gain Apo - E and APo C- II from HDL in the plasma
- Apo C - II activates lipoprotein lipase (LPL) located on capillary endothelia
- LPL catalyzes the conversion of TAGS to free fatty acids and glycerol
- fatty acids are taken up by the tissues and metabolized
• Predict the consequences of an excess of chylomicrons or VLDL on serum TAGs
Chylomicrons and VLDL transport TAGS and cholesterol into adipose tissue. An excess of either could cause atherosclerosis by causing cholesterol to build up in artery walls.
Predict whether the concentration of chylomicrons is a better indicator of
consumption of dietary carbohydrates or dietary fat. Do the same for VLDL.
Chylomicron should be an indicator for fat consumption. Chylomicrons form during absorption of lipids.
VLDL should be an indicator for carbohydrate consumption. VLDL is made up of triglycerides which require glycerol to be formed, and glycerol can be obtained from glucose.
What does lipoprotein lipase do?
Where do released FAs go following action of lipoprotein lipase?
hydrolyzes the fatty acids from the TAGs in VLDL and chylomicrons
may be metabolized by fatty acid oxidation or incorporated into adipose tissue TAGs
• Identify the apoprotein component, common to both VLDL and chylomicrons, that is responsible for activating lipoprotein lipase.
An apolipoprotein of _____ and ___ binds to a cell membrane receptor to remove ___ from circulation?
- Apo-CII
- chylomicrons and IDL,
chylomicron remnant and IDL
What is the basic function of LDL and HDL?
Compare the roles of LDL and HDL in cholesterol transport LDL:
- cholesterol transporter
- LDL: Delivers cholesterol to the liver and other cells, including steroidogenic cells.
HDL: Accepts cholesterol from peripheral cells, esterifies it, and transports CEs to liver. Exchanges CE for TAG in VLDL, IDL and chylomicron remnants. Inhibits LDL oxidation through enzymes like paraoxonase. Reserboid for circulating apoproteins.
Identify the apoprotein of LDL that binds to the LDL receptor
Explain the role of LDL receptors and clathrin-coated pits in removal of LDL.
- Apo B-100
- LDL receptors are present in clathrin-coated pits on the cell surface, which pinch off to form clathrin-coated vesicles inside the cell. This allows LDL-cholesterol to go through endocytosis that prevents LDL from diffusing out the membrane surface. The clathrin coat is shed once the vesicle enters the endosome.
Predict the consequences of a defect in functional LDL receptors on cholesterol biosynthesis, formation of intracellular cholesterol esters, and serum cholesterol levels.
It would decrease cholesterol biosynthesis and formation of intracellular cholesterol esters, but increase serum cholesterol levels.
Explain how HDL’s are involved with “reverse cholesterol transport”
HDLs are made in the liver in a discoid shape and have Apo A-1, LCAT, and phospholipids.
The convert to spheroid shape.
Free cholesterol + HDL –> HDL3 then HDL2
LCAT esterifies cholesterol via Apo-A1
HDL brings cholesterol to liver by 2 mechanisms:
CETP mediates transfer of CE from HDL to VLDL/IDL/CyM remnant in exchange for TAG. Spherical HDL is then taken by liver by Apo A1 binding to SR-BI.
What is used as a predictor of atheroscerosis and coronary heart disease?
Explain the proposed mechanism of action for drugs that are used to lower
serum cholesterol levels .
- Serum cholesterol
2. Statins are a class of drugs used to lower cholesterol levels by inhibiting HMG-CoA reductase
VLDL transport ____ and ____ that are synthesized (endogenously/exogenously).
- TAGS
- Cholesterol
- endogenously
What is the target of STATINS?
HMG Co - A Reductase
- inhibits the synthesis of cholesterol
Removal of LDL requires what?
A functional LDL receptor
What directly interacts with LDL for receptor INDEPENDENT uptake?
When is this important?
Macrophages
- when cholesterol levels are HIGH
What is down regulated when cholesterol levels are high?
High affinity LDL receptors involved with LDL receptor mediated uptake of cholesterol
______ cholesterol can be oxidized by oxidants.
What are 3 important anti-oxidants?
LDL cholesterol
- Vitamin E
- Vitamin C (ascorbic acid)
- Vitamin A (beta-carotene)
What can take up oxidized LDL?
What increases this?
- Macrophages
2. SMOKING increases uptake of oxidized LDL by macrophages
What do cholesterol laden macrophages become?
Foam cells
What happens when foam cells accumulate?
They release cytokines that stimulate the proliferation of smooth muscle cells and calcification of plaque
What is the result of continued uptake of oxidized LDL?
Coronary Artery Disease and Atherosclerosis
What are 2 atheroprotective effects of HDL?
- HDL contains enzymes that inhibit LDL oxidation in blood vessels
- HDL increases NO synthesis by endothelial cells
Compare the following for HDL and LDL
- Size
- Protein content
- Function
HDL:
- Size - SMALLER
- Protein content - more protein
- Function - removes cholesterol from tissues
LDL:
- Size - LARGER
- Protein content - less protein
- Function - take cholesterol TO the liver
What type of cholesterol is formed in the liver and contains atheroprotective enzymes like PARAOXANASE that inhibit LDL oxidation?
HDL
