Biochem Final Review Flashcards
What is the function of cholesterol in the body?
component of cell membranes that modulate fluidity
in specialized tissue as a precursor of bile acids, steroid hormones, and vitamin D
ensure continuous supply of transport, biosynthetic and regulatory mechanisms
What organ plays the central role in regulations of the body’s cholesterol homeostasis?
liver
What layer of the membrane is cholesterol found?
both layers
What are the sources of cholesterol that enter the liver’s cholesterol pool?
dietary cholesterol
de novo synthesis by extrahepatic tissues
de novo sythesis by the lvier itself
How is cholesterol eliminated from the liver?
as unmodified cholesterol in the bile
converted to bile salts that are secreted into the intestinal lumen
sent to the peripheral tissues
With good circulation, how much cholesterol would we retain from intestinal digestion?
about 90%
What are the consequences of cholesterol imbalance?
deposition in the tissues particularly in the endothelial lining of blood vessels that lead to plaque formation causing narrowing blood vessels, atherosclerosis and increased CAD risk
When transported around the body, the plasma cholesterol form is _______.
esterified in lipoproteins
Detail cholesterol synthesis.
synthesized by virtually all tissues, esp the liver, intestine, adrenal cortex and reproductive tissues
all carbons are provided by acetate
NADPH is the reducing equivalents
synthesis occurs in the cytoplasma where the enzymes are in the cytosol and ER
The pathway is responsive to cholesterol conc such that regulatory mechanisms exist to balance the rate of cholesterol synthesis within the body against the rate of excretion
Because the de novo synthesis takes alot of effort, we try to retain as much as possible.
Detail how HMG-CoA is synthesized
2 acetyl CoAs are put together by thiolase and a third is added to make HMG CoA by HMG-CoA synthase
this is the first two steps of cholesterol synthesis
What is the rate-limiting step of cholesterol?
HMG CoA reductase that takes HMG CoA to mevalonic acid using two NADPH equivalents
What are the regulation points of cholesterol synthesis?
- SREBP controls the HMG CoA reductase gene such that bound SREBP causes increased expression when cholesterol levels are low
- protein and mRNA stability where cholesterol presence decreases the stability and increases the degradation
- phosphorylation/ dephosphorylation where inactivation/activation is regulated by AMP where high AMP (means low ATP from cholesterol synthesis) activates dephosphorylation?
- hormonal regulation where insulin favors cholesterol synthesis from upregulated HMG CoA and glucagon does the opposite
What is lovastatin and how does it work?
lovastatin is a statin prodrug that is a structural analog of HMGCoA mimicking the intermediate in the reduction by HMG CoA reductase, but as the competitive inhibitor, lovastatin binds several time more tightly than HMG CoA from a higher affinity for the reductase enzyme
How does dietary cholesterol affect the body’s synthesis of cholesterol?
eat too much cholesterol decreases synthesis and vice versa
To what are the rings of cholesterol metabolized in humans?
carbon dioxide and water
How does the sterol nucleus of cholesterol get eliminated from the body?
it is converted to bile acids and bile salts that are secreted in the feces
Detail bile acids.
can be cholic acids with three hydroxyls or chenodeoxycholic acids with two hydroxyls that are in alpha orientations (below plane) so that there are two faces (polar/nonpolar) making them amphiphatic
the carboxyl group has a pKa of 6 so that it isn’t fully ionized at physiological pH which is why acids are most common
How does the bile acid become a bile salt?
through modification in the liver where a glycine or taurine is added by an amide bond
Which is more acidic and fully ionized at physiological pH (salts or acids)?
acids
Which is found in bile (acids or salts)?
ONLY BILE SALTS because they are more effective detergents
How are individuals with genetic deficiencies in the conversion of cholesterol to bile acids treated?
with exogenously supplied chendodeoxycholic acid
What is the order of synthesis in the liver of cholesterol to salts and what is secreted?
cholesterol to bile acids to bile salts
cholesterol with bile salts are secreted
Bile salts that are secreted into the intestines are
efficiently reabsorbed (more than 95%) and reused where the absorption primarily occurs in the ileum and very little is lost and very little is synthesized each day
Bile acid sequestrants such as cholestyramine ___ bile in the gut, ____ their reabsorption, and ____ excretion.
bind
prevent
promote