cholesterol synthesis Flashcards
where does cholesterol synthesis occurs?
ER
cytosol
overall process of 1 cholesterol involves how many? acetylcoA ATP NADPH enzymes
18 acetylcoA
36 ATP
20 NADPH
12 enzymes
what are the inhibitors of HMG coA reductase?
bile acids
cholesterol
mevalonate
(statins!!)
what does phosphorylation do to HMG coA reductase?
inactivation
by AMPK- which sense high AMP levels, means less ATP
how does insulin effects cholesterol synthesis?
activates it because it promotes dephosphorylation of HMG coA reductase
what family of proteins controll the number of HMG coA reductase?
SREBP
what happens to the insig-SCAP-SREBP when sterol levels are high?
insig-SCAP-SREBP complex is retained in the ER membrane
what is LXR? what activates it?
nuclear transcription factor
activated by oxysterol ligands (reflecting high cholesterol levels)
what happens to LXR when it binds oxysterol ligand?
LXR form heterodimer with RXR
write down what will happen when LXR-RXR dimerize:
they will activate transcription of
- acetyl co A carboxylase
- FA synthase
- cyt. P-450, CYP7A1
- Apo that are involved in cholesterol transport
- ABC transporters
what will activate ACAT?
high intracellular conc of cholesterol
ACAT will increase esterification of cholesterol for storage
what will high cholesterol levels will do to the transcription of LDL receptors?
diminish transcription -> reducing production of the receptor -> reducing the uptake of cholesterol from the blood
write down levels of regulation of HMG coA reductase (4)
- protein degregation (through insig)
- reversible covalent modification (by AMPK)
- gene transcription (by SREBP-SCAP)
- inhibition of translation (by mevalonate)
what is the long term modification of HMG coA reductase?
inhibition of translation (by mevalonate)
what will lower cholesterol levels (when intracellular cholesterol is high) ?
- insig-SREBP-SCAP complex is deactivated (stay in ER)
- LDL receptor transcription is reduced
- miR-33a is inhibited by cholesterol
- LXR-RXR dimer is activated -> promote bile formation and cholesterol transport
- ACAT activation is increased
what is the job of ABCA1/ABCG1 ?
transport cholesterol out of the cell
what is the job of NPC1L1 ?
uptake of free cholesterol into enterocytes of the intestine
what is the job of ACAT ?
esterify cholesterol to CE in the ER membrane insidr the cell
what is the job of LCAT ?
esterify cholesterol to CE in the HDL particle
what is reversed cholesterol transport????
who is the main lipoprotein?
- mechanism by which the body removes excess cholesterol from peripheral tissues and delivers them to the liver!!!
- HDL!
how does cholesterol from non hepatic cell being transferred to HDL?
by the ABCA1
what Apo will bind LDL?
Apo B100
Apo E
how do LDL taken up?
by endocytosis
what does LDL conc in the blood depends on?
amount of LDL receptors
