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43 Cards in this Set

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What is the rate limiting step in Cholesterol synthesis?
HMG CoA ---> Mevalonic Acid catalized by HMG CoA Reductase.
What is the difference between Cholesterol and Cholesterol Ester? Why does it matter?
Cholesterol + one free fatty acid = Cholesterol Ester (CE).
CE is the storage form of cholesterol in cells.
What step in Cholesterol synthesis do statins inhibit?
The Rate Limiting Step: HMG CoA --> Mevalonic Acid by HMG CoA Reductase.
What tissue makes cholesterol?
All tissue synthesize cholesterol but 10-20% of cholesterol synthesis happens in the liver.
HMG CoA Reductase:
What up-regulates the synthesis of HMG CoA Reductase?
Low Cholesterol signals the Sterol Regulatory Element-Binding Protein (SREBP) to travel to the nucleus and increase the transcription of the HMG CoA Reductase gene.
HMG CoA Reductase:
What increases the activity of HMG CoA Reductase?
Insulin via Protein Phosphatase. So, it is more active when de-phosphorylated.
HMG CoA Reductase:
What decreses the activity of HMG CoA Reductase?
Increased cholesterol decreases protein stability.
Also, phosphorylation of enzyme decreases its activity.
Trace a cholesterol molecule in the liver to Micelle formation in the gut.
Cholesterol --> Bile Acid --> Bile Salt --> GI --> Micelle formation.
The first step is done in the liver by 7-Alpha-Hydroxylase.
What is the only significant mechanism for cholesterol excretion in the body?
Bile salts. The liver must then synthesize more blie acids from cholesterol.
Where do Chytomicrons (CM) form?
Intestine
The Chylomicron (CM) acquires two proteins in the blood stream. Which proteins are they? Who gives those proteins to the CM?
ApoE and ApoCII.

HDL gives the CM in the blood stream those two proteins.
Why are ApoE and ApoCII needed in the CM/CM-Remnants?
ApoE is needed because it is recognized by LDL-R Related Protein receptor in the liver.

ApoCII is needed because it is a co-factor for Lipoprotein Lipase (LPL) which degrades TC.
Which protein is unique to the Chylomicron/CM-Remnant?
Apo48
Which lipoprotein has the highest percentage of Triglycerides?
CM
Which lipoprotein has the lowest percentage of Triglycerides?
LDL and HDL
Which lipoprotein has the highest percentage of Cholesterol?
LDL
Which lipoprotein has the lowest percentage of Cholesterol?
Chylomicron
What is the goal of VLDL/IDL/LDL lipoproteins?
To release contents into tissue.
Where is VLDL made?
In the liver.
Which is the main protein of VLDL?
ApoB100 which indicates that it was made in the liver.
What proteins does VLDL acquire as it matures in the blood?
ApoE and ApoCII, again donated by HDL.
What is the purpose of ApoCII in VLDL?
To activate LPL so that VLDL may turn into IDL.
What makes up the bulk of VLDL?
TG at 65%
How does IDL become LDL?
Two ways:
1) Further hydrolyzed by LPL and Hepatic Lipase (LP).
2) It also trades TG for CE with HDL via Cholesterol Ester Transfer Protein (CETP)
What is the fate of LDL?
Delivers Cholesterol to tissues by endocytosis. The tissue recognizes ApoB100 or ApoE via LDL Receptor.
Where do we find a lot of LDL-Receptors?
Adrenal glands, gonads.
What is a lipoprotein(a)?
LDL with Apo(a) and ApoB100 liked together via a disulfide bond.
Which proteins does the LDL-Receptor bind?
ApoB100 and ApoE
What controls the expression of LDL-R gene?
SREBP
Why does the LDL Receptor Related Protein does not bind LDL?
Because LDL has lost its ApoE. It only has ApoB100. ApoB100 is not recognized by LDL Receptor Related Protein.
What happens if there are mutations in the LDL-Receptor?
LDL-Receptor binds ApoB100 &/or ApoE. So, it binds LDL. If it cannot bind LDL then the result would be high levels of LDL in the blood.
Where is HDL made?
In both liver and intestines.
What is the goal of HDL?
To take up free cholesterol from tissues to deliver it back to the liver.
What does HDL do the free cholesterol?
it turns it into Cholesterol Ester via LCAT.
How can HDL transfer cholesterol back to liver?
Via SRB1
How can HDL transfer cholesterol to tissues other than liver?
By trading Cholesterol for TG with LDL via CETransfer Protein.
What happens to small and dense HDL particles?
Get excreted by kidney
Where do we find ApoA1? What is its purpose?
Found in HDL.
It has many purposes:
1) structural protein
2) LCAT co-factor (LCAT converts free cholesterol into cholesterol ester)
3) Binds SR-B1 (to deliver CE to liver, adrenal glands, gonads.)
What is ABC1?
Transports FC out of cells to be picked up by HDL
why do we use a fasting blood sample for a lipid profile?
To eliminate chylomicrons
How do you estimate LDL?
LDL = TG - ( HDL + [ TG / 5 ] )
Under condition that TG < 400
What are five factors that can affect LDL blood levels?
1) Increased VLDL synthesis
2) Down-regulation of LDLR
3) Increased ApoE-containing molecules that compete for LDLR
4) Defective or decresed expression of LDLR
5) Defective ApoB100
What is the name of HMG CoA Reductase Inhibitors often prescribed?
Statins