Cholesterol (Deev) Flashcards
What is one major function of cholesterol?
precursor for steroid hormones.
Organic compound with four fused rings arranged in a specific ABCD configuration.
Steroids
A subgroup of steroids with a hydroxyl group at the 3 position of the A-ring.
hydroxyl
Highly hydrophobic compound, and is the major sterol in animal tissues.
Cholesterol
Most important functions of Cholesterol:
structural component
maintain integrity and fluidity
enables cells to dispense within the cell
lipid rafts
What 3 things are involved with lipid rafts?
sphingolipids
cholesterol
phospholipids??
Cholesterol is a precursor for synthesis of what 3 things:
Bile salts
Steroid hormones
Vitamin D
Free cholesterol (unesterified) is found in ________ of all animal cells
membranes
_________ cholesterol (plasma cholesterol) is not found in membranes, bound to a protein that can solubilize them and transport them for the body.
Esterified
True False: Most cells can synthesize cholesterol
True
________ is the central organ that controls the overall cholesterol homeostasis.
Liver
Sources of liver cholesterol:
De novo synthesis
Diet
Delivered via HDLs
What are the routes for cholesterol clearance from the liver to the rest of the body?
Secretion into VLDL/ LDL
Cholesterol is secreted as free cholesterol into bile and converted to bile acids/salts
Lipid depositions can lead to __________ over time and narrowing of blood vessels.
plaque formation
Narrowing of blood vessels is called _________.
Atherosclerosis
Atherosclerosis (narrowing of blood vessels) can cause
increased risk of cardio- cerebro- and peripheral vascular disease
Narrowing of blood vessels is called _________, a potentially life threatening disease.
Atherosclerosis
Atherosclerosis (narrowing of blood vessels) can cause
increased risk of cardio- cerebro- and peripheral vascular disease
What are the substrates for cholesterol synthesis?
Acetyl CoA- to build carbons of cholesterol
NADPH- reducing equivalents
ATP- as energy
Why do low fat diets not lower cholesterol?
Low fat diets usually have higher carbohydrates, so there is more glucose
What is the enzyme important for conversion of Acetyl CoA to HMG CoA:
HMG-CoA synthase
2 isoenzyme forms:
-cytosolic- used to make cholesterol
-mitochondrial- used to make ketone bodies
What is the enzyme that catalyzes the synthesis of mevalonate? Rate limiting key regulatory step. (WE HAVE TO KNOW THIS ENZYME)
HMG-CoA reductase
Statin drugs are a big group of compounds that are considered ___________ inhibitors (most prescribed drugs in US)
competitive
How many molecules of acetyl CoA are required to make one molecule of cholesterol?
18 Acetyl CoAs for 1 cholesterol
Can cholesterol be metabolized to CO2 like sugars and fats? Why?
No, no enzyme for reverse reaction.
Where does synthesis of cholesterol take place?
Cytoplasm
Regulation of HMG CoA reductase:
Regulation of levels of the enzyme protein product
Sterol independent covalent modifications- phosphorylation and dephosphorylation via AMPK
Hormonal regulation- insulin and thyroxine upregulate HMG CoA reductase, glucagon and glucocorticoids downregulate it.
If levels of sterols suddenly drop then _______ transcription factor will bind in order to start producing the sterol ring.
SREBP
Cholesterol ring structure cannot be metabolized to ________ and ______ in humans.
CO2 and H2O
Cholesterol is secreted into _____ and excreted from the body.
Bile
> 60% of Bile is made up of _____.
bile salts
How does cholesterol, bile acids, and bile work together?
Bile acids are the precursor for the synthesis of bile salts, and are produced in liver cells from cholesterol.
Cholesterol–> Bile Acids–> Bile salts
What is a watery mixture of organic and inorganic compounds produced by the liver to help with digestion of lipids in the small intestine?
Bile
Cholelithiasis (gall stones ) are derived from ________.
Cholesterol
Too little ________ or too much ________ causes gall stones.
Bile salts
Cholesterol
Possible causes of gall stones leading to lower bile salts or high cholesterol.
Inefficient enterohepatic cycling
liver dysfunction
Spherical macromolecular complexes of lipids and specific proteins (apolipoproteins)
Lipoproteins
Lipoproteins function is to transport:
cholesterol, fats and fat-soluble compounds in the plasma.
______ transports dietary lipids, produced in enterocytes.
Chylomicrons
What is VLDL?
Very low density lipoproteins transport newly synthesized lipids produced in hepatocytes.
What is LDL?
Low density Lipoproteins- transport cholesterol to peripheral tissues
What is HDL?
High density lipoproteins. transport cholesterol from periphery to the liver.
How are lipoproteins arranged?
One layer of phospholipids (PC and SM)
Hydrophilic head and hydrophobic fatty acid tails.
There are 11 different types of ___________ _________.
Amphipathic apolipoproteins
What are the largest, least dense, and highest fat percentage of all lipoproteins?
Chylomicrons
What are smaller and more dense than chylomicrons and are produced in hepatocytes (liver cells) to distribute fat away from the liver to peripheral tissues.
VLDLs
What makes up the highest percentage of cholesterol? These are the bad cholesterols.
LDLs
This is the second highest percentage of cholesterol ~25% which brings peripheral cholesterol to the liver. Good cholesterol.
HDLs
Size and density of ________ are routinely used in plasma lipid profiling, have to be in fasted patient to be accurate.
lipoproteins
Which of the lipoproteins would you expect to vary based on recent meals?
Chylomicrons
VLDLs
because they are very shortly lived particles, degraded quickly.
Chylomicrons go to the ______ (hospital) and _______ of intestinal mucosal cells, using _______ as scaffold protein.
ER
Golgi
Apo B48
Lipids are transferred to ApoB-48 via a _______.
microsomal Transfer Protein (MTP)
_________ is the central organ for lipoprotein pathways.
liver
If there is excess free cholesterol:
converted to CE by ACAT (acyl CoA: cholesterol acyltransferase) and stored in lipid droplets
_______ are very sensitive to oxidizing agents.
Lipids
3 factors increasing propensity for producing modified LDL in the circulation:
High blood sugar
Oxidative stress
Chemicals in tobacco smoke
HDL does reverse ______ transport.
Cholesterol, therefore HDL is good cholesterol
This disease is deficiency of Apo CII or Lipoprotein lipase (LPL)
Type 1 hyperlipoproteinemia
Disease that is a defect in LDL receptor
Type IIa hyperlipidemia
Disease that is a defect in Apo E protein synthesis
Type III hyperlipoproteinemia
This disease is a defect in the microsomal transfer protein (MTP)…
Progressive degeneration of the retina that can progress to near-blindness (due to dificiency of Vitamin A, retinol)
Abetalipoproteinemia (Bassen Kornzweig syndrome)
