Cholesterol Biosynthesis Flashcards
Example of bad cholesterol
LDL (Low density lipoprotein)
Composition of a cholesterol molecule (2 parts)
Steroid nucleus (4 fused rings) Hydrocarbon tail (possible long chain FA at C3 if esterified)
What makes a cholesterol ester
A long chain FA added to the A ring at Carbon #3
Cholesterol esters are highly (hydrophilic/phobic)
Hydrophobic
% of cholesterols that are esterified
70%
_________ are in the interior of the lipoproteins, while ________ is on the surface
Cholesterol esters; free cholesterol
Roles of cholesterol
Membrane composition Signaling Bile acids Steroid hormones Vitamin D Embryo formation
Greatest synthetic site of cholesterol
Liver (80%)
Rate-limiting step in cholesterol synthesis
HMG CoA reductase
HMG CoA reductase activity is inhibited by ____________
free, non-esterified cholesterol
Insulin (inhibits/stimulates) gene expression of HMG CoA reductase
Stimulates (promotes storage as cholesterol)
Class of drugs that are structural analogs of HMG CoA; bind and competitively inhibit enzyme
Statin drugs
HMG CoA reductase sits on what membrane?
Endoplasmic Reticulum
Cholesterol derivative involved in oxidative phosphorylation
Coenzyme Q10
Cholesterol derivative involved in synthesis of glycoproteins
Dolichol phosphate
Cholesterol derivatives involved in signal transduction
Rho and Ras
In cholesterol-depleted cells, this protein binds to SREBPs and mediates their transport from the ER to the Golgi apparatus. The SREBPs are then proteolytically cleaved and stimulate sterol biosynthesis.
SCAP
High cholesterol can create _______, which can inhibit SCAP and prevent cholesterol biosynthesis via HMG CoA
Oxysterols
LDL receptors are down-regulated by…
free cholesterol
Role of LDL
provide cholesterol to peripheral tissue
return it to the liver
LDL receptors
Apo B100
Apo E
Enzyme that esterifies cholesterols for storage
ACAT
A diet high in saturated fats can have what enzymatic effects?
Inhibit ACAT (can only use unsaturated) Reduced LDL
A diet low in fiber can have what enzymatic effects?
Fiber binds bile acids in intestine, increasing clearance.
Low fiber means increased bile acids circulating, inhibiting 7a hydroxylase
Rate limiting step in bile acid synthesis
7a-hydroxylation
Primary bile acids made by liver
Cholic acid
Chenodeoxycholic acids
Why are bile acids good emulsifiers
have polar and nonpolar portions
Only significant mechanism for eliminating cholesterol from the body
Conversion into bile
What regulates 7a-hydroxylase activity?
cholesterol (activates) bile acids (inhibited)
% of bile acids that are reabsorbed in enterohepatic circulation
99%
Drug that inhibits cholesterol absorption in small intestine
Etzetimibe