lipoprotein metabolism - biochem Flashcards
cholesterol is a precursor for what
steroid hormones, bile acids, vit. D
what is the rate-limiting step of de novo cholesterol synthesis
HMG-CoA
–(HMGCR)–>
mevalonate
->
->
->
cholesterol
what enzyme is the target of cholesterol-lowering statin drugs
HMGCR
what is SREBP
a TF that activates HMGCR
how is HMGCR inhibited through negative feedback
SREBP is inhibited by cholesterol
liver is distribution hub of _____
cholesterol
reaction for cholesterol ester synthesis in cells
free cholesterol
–(ACAT)–>
cholesterol ester
reaction for cholesterol ester synthesis in plasma
free cholesterol
–(LCAT)–>
cholesterol ester
free cholesterol
-polarity
-function
amphipathic
membrane structure
cholesterol ester (CE)
-polarity
-function & where
-transported how
hydrophobic
storage
in lipid droplets within cells
transported in plasma inside lipoprotein particles
how do lipoprotein particles transport cholesterol
in the core of lipoprotein particles in the form of cholesterol ester
lipoprotein composition
integral apoproteins
-definition
-function
structural component of lipoproteins (can’t be removed)
gives “identity” to the lipoprotein
peripheral apoproteins
-definition
-function
transferable between lipoproteins
controls activity of lipoprotein-metabolizing enzymes
TG-rich lipoproteins
cholesterol-rich lipoproteins
lipoprotein CM is _____ & contains _____
TG-rich
ApoB-48
ApoE
ApoC-II
integral apoproteins
ApoB-48
ApoB-100
Apo(a)
ApoA-I
peripheral apoproteins
ApoE
ApoC-II
lipoprotein VLDL is _____ & contains _____
TG-rich
ApoB-100
ApoE
ApoC-II
lipoprotein CMR is _____ & contains _____
cholesterol-rich
ApoB-48
ApoE
lipoprotein IDL is _____ & contains _____
cholesterol-rich
ApoB-100
ApoE
lipoprotein LDL is _____ & contains _____
cholesterol-rich
ApoB-100
lipoprotein Lp(a) is _____ & contains _____
cholesterol-rich
ApoB-100
Apo(a)
lipoprotein HDL is _____ & contains _____
cholesterol-rich
ApoA-I
ApoE
ApoC-II
lipoprotein Lp(a) has high _____, contributes to _____, & how is it shown in labs
high heterogeneity
contributes to atherosclerosis
in labs it is lumped in with LDL
why does hydrolysis of remaining TG not occur in CMR (which would produce additional smaller lipoproteins)
bc ApoB-48 is too short to bind an LDL receptor
how are cholesterol-rich lipoproteins produced from TG-rich lipoproteins
CM, VLDL
–(LPL hydrolyzes TG)–>
CMR, IDL
how is LDL produced from IDL
hydrolysis of remaining TG in IDL occurs
what Apo protein does the liver express
only ApoB100
general pathway of cholesterol in the body
dietary cholesterol
->
absorbed in intestines
->
delivered to liver
->
excess hepatic cholesterol (as bile acids) is transported back to intestine for fecal excretion
detailed pathway of cholesterol absorption into chylomicrons
dietary cholesterol + plant sterols (sitosterols) taken into enterocytes via NPC1L1 (cholesterol transport protein)
->
cholesterol esterified by ACAT to form cholesterol ester
->
chylomicron formed
->
chylomicron exocytosed from enterocyte to the lymph and into the circulation
->
plant sterols leave enterocyte & back to where they started via ABCG5/8 (sterol efflux protein)
components of a chylomicron
cholesterol ester
TAG
PL (phospholipid)
fat-soluble vitamins
-> MTTP loads all of them onto ApoB-48
what is a deficiency in ABCG5/8 called
sitosterolemia
what happens if NPC1L1 (Ezetimibe) is inhibited
decreased cholesterol absorption
->
decreased plasma cholesterol
how is dietary cholesterol delivered to the liver
by CM remnants
LDLR pathway
LDL binds to LDLR through AopB-100
->
this complex taken in by endocytosis
->
LDL & LDLR separate in endosome
->
LDLR recycled back to plasma membrane
->
LDL goes to lysosomes & enters cellular cholesterol pool
v intracellular cholesterol = ___ LDLR = ___ LDL-c
^ LDLR, v LDL-c
^ intracellular cholesterol = ___ LDLR = ___ LDL-c
v LDLR, ^ LDL-c
what are the main bile acids that cholesterol is converted into
cholic & chenodeoxycholic acids
what is the rate-limiting enzyme of bile acid synthesis
CYP7A1
how is bile acid synthesis regulated
negative feedback of bile acids inhibits CYP7A1 via transcription factor
how are bile acids delivered to duodenum
via bile
% of excreted bile acids that are reabsorbed, & how are they reabsorbed
95% reabsorbed to liver through portal vein
reverse cholesterol transport mechanism
LDL enters intima layer of artery
->
LDL oxidized by free radicals
->
gobbled up by macrophages, makes foam cells
->
HDL causes reverse cholesterol transport from artery to liver
what does HDL protect against by initiating reverse cholesterol transport
atherosclerosis
mechanism if foam cells accumulate in artery
atherosclerotic plaque build up
->
blood vessels narrow
->
ischemia, MI
mechanism of how bile acid reabsorption inhibition lowers cholesterol
bile acid reabsorption inhibition
->
less bile acid in liver
->
CYP7A1 no longer inhibited
->
more cholesterol converted to bile acid
->
less cholesterol in liver
->
causes more expression of LDLR on surface
->
more LDL uptake
->
lower plasma LDL
