lecture 8: cholesterol synthesis Flashcards
what is the common factor of cholesterol-containing foods?
animal sources - comes from liver
cholesterol fluidity
increases fluidity in colder temperatures
decreases fluidity in warmer temperatures
atherosclerosis
thickening of arteries from deposition of cholesterol and cholesterol lipoproteins in arteries
chylomicrons
transport dietary lipids throughout the body
how does the liver repackage cholesterol? how is it taken up?
repackage from chylomicrons into VLDL > IDL, LDL
most tissues take up LDL as cholesterol source
cholesterol synthesis site
liver and intestine are major sites
occurs in the cytosol, closely associated with ER
substrate for cholesterol synthesis
acetyl-CoA
conversion of acetyl-CoA to mevalonate
three 2C acetyl-CoA condensed to form 6C HMG-CoA
HMG-CoA reductase to mevalonate
cholesterol synthesis steps
conversion of acetyl-CoA to mevalonate
mevalonate to isoprenoids (5C)
isoprenoids to squalene, cholesterol, lanosterol
intermediates reduced by NADPH
primary target of cholesterol regulation
HMG-CoA reductase (controls production of melavonate)
HMG-CoA reductase
anchored to ER membrane
negative feedback from mevalonate and cholesterol
inhibited by statins (lipid lowering drugs)
sterol regulatory element-binding protein (SREBP) and regulation of transcription
sterol regulatory element (SRE) controls transcription, bound by SREBP to promoter region of genes
SREBPs induce transcription of genes involved in cholesterol metabolism and TAG/FA synthesis
when cholesterol levels in ER membrane is low…
SCAP (SREBP cleavage-activating protein) binds to component of COPII coat proteins > vesicles bud off ER and sent to golgi
SREBP cleaved, releasing active form
when cholesterol levels are high…
cholesterol binding to SCAP causes SCAP to bind to Insig > prevents SCAP from interacting with COPII (cannot be sent to golgi, active SREBP not released)
HMG-CoA reductase degredation
high cholesterol > HMG-CoA reductase binds to insig > ubiquitination and proteosomal degradation