Cholesterol is a structural component of cell membranes and a precursor for these important things in our body?
Bile acids
Steroid Hormones
Vitamine D
Is Cholesterol hydrophobic or hydrophilic?
Hydrophobic
Cholesterol is found where in the body and in what form?
Blood plasma
Esterified form with a fatty acid attached at carbon 3
All the carbons for cholesterol synthesis are produced from what biochemical compound?
Acetate
What compound provides the reducing power for cholesterol synthesis?
NADPH
Where does synthesis of cholesterol occur in the body?
Cytosol of the cell and in the SER
What molecules are combined to form Acetoacetyl CoA?
Acetyl CoA - 2 of them
When we add a third Acetyl CoA to acetoacetyl the produced formed is called?
HMG-CoA
What enzyme is responsible for the synthesis of the HMG-CoA?
HMG-CoA Synthase
When HMG-CoA synthase is in the mitochondria it is used to make?
Ketone Bodies
What does the enzyme HMG-CoA reductase do?
Reduces HMG-CoA to Melavonate
What is unique about the reduction step of HMG-CoA?
Rate limiting and irreversible step in cholesterol synthesis!
Where in the cell do we find the HMG-CoA reductase enzyme?
SER
How many NADPH is used to form melavonate from HMG-CoA?
2
What is a big player in the regulation of Choleseterol Synthesis?
Sterol-dependent regulation of gene expression
In the sterol-dependent regulation of cholesterol the expression of the gene for HMG CoA reductase is controlled by:
The transcription factor SREBP (sterol regulatory element-binding protein-2)
Where in the cell do we find the SREBP?
Integral protein of the ER membrane
Name the other membrane protein that SREBP is associated with?
SCAP (SREBP cleavage activating protein)
What would cause the SREBP-SCAP complex to be sent out of the ER to the Golgi?
Low sterol levels of the cell
What happens to the SREBP-SCAP complex once in the Golgi?
- 2 proteases cleave the SREBP from SCAP
- SREBP moves to the nucleus and binds the SRE
- This binding up regulates the synthesis of HMG-CoA reductase.
This enzyme controls the HMG-CoA reductase covalently
Adenosine Monophosphate-activated protein kinase
What form of the HMG-CoA is inactive?
Phosphorylated
Dephosphorylation will affect the HMG-CoA how?
Activates the enzyme
An increase in these hormones will favour the up regulation of HMg-CoA reductase:
Insulin
Thyroxine
How do glucagon and glucocorticoids effect cholesterol synthesis?
Down regulation of HMG-CoA reductase
Why is it called a bile acid?
It has a terminal carboxyl group with a pKa of 6
T or F
Bile Salts an amphipathic
True
What makes bile salts amphipathic?
Hydroxyl group lies beneath the plane of the molecule while the methyl group lie above the plane of the molecule
What are the most common bile acids?
Cholic Acid
Chenodeoxycholic Acid
Where are bile acids synthesized?
Liver
What is the rate limiting step of bile acid synthesis?
The introduction of a hydroxyl group at carbon 7 of the steroid nucleus by the enzyme cholesterol-7-alpha-hydoxylase
What will down regulate Cholesterol-7-alpha hydroxylase?
Cholic Acid
What happens to the bile acids before they leave the liver?
They are conjugated with either glycine or taurine
Only _____ _____ are found in bile.
Bile salts
What is the only effective mechanism for the excretion of cholesterol in the body?
Bile Salts
How can the taurine and glycine be removed from the bile salts when the body wants to recycle?
Bacteria in the intestine
How are secondary bile acids formed?
The bacteria in the intestine will remove the hydroxyl group of the bile acid producing deoxycholic and lilocholic acid from chenodeoxycholic acid.
This percent of bile acids secreted in the intestine will be absorbed?
95%
Where are bile acids primarily absorbed?
Ileum via Na+ bile salt co-transporter
Cholesterol secretion into the bile must be accompanied by the secretion of these two compounds too
Phospholipids and bile salts
What happens if the cholesterol secretion process is disrupted and more cholesterol is secreted?
The cholesterol may precipitate in the gallbladder leading to gallstone disease - cholelithiases
The fat soluble vitamins are?
ADEK
Cholesterol is one of many _____________
Isoprenoids
This vitamin is important for calcium homeostasis?
Vit D3
This steroid hormone regulates the salt and water balance
Mineralocorticoids
This steroid hormone has a big role in regulation of metabolism…
Glucocorticoids
How many ATP are used to make squalene?
18
The short term regulation of HMG-CoA reductase is?
Phosphorylation