Lipoprotein Metabolism Flashcards
What is the only way to excrete cholesterol?
bile
why are fats packaged into lipoprotien?
polar capsule allows them to move through water
apolipoproteins
proteins attached to the outer shell of a lipoprotein
what lipoproteins are high in triglycerides?
VLDL and chylomicron
what lipoproteins are high in cholesterol esters?
LDL and HDL
Apo A-1
associated with HDL
activates LCAT
Apo B-48
associated with chylomicrons
Mature chylomicrons
gain Apo C-11 and Apo E in addition to Apo B-48 which is present on all chylomicrons
Apo B-100
associated with VLDL and LDL
C-terminal of B-100 binds to LDL receptor
What apoproteins do nascent LDL have ?
B-100, C-11 and E
What apoproteins do mature LDL have?
B-100
What apoproteins do nascent VLDL have?
B-100
What apoproteins do mature VLDL have?
B-100, C-II and E
What apoproteins do mature HDL have?
A-1, C-11 and E
*nascent HDL only have A-1
What is the source of C-11 and E for chylomicrons?
HDL
What receptor do chylomicrons end up solely expressing?
they solely express E
Apoprotein E and binding
able to bind the remnant receptors on liver
allows chlyomicron remnants to bind to liver
LDL function
give cholesterol to peripheral tissues
HDL function
retrieve excess cholesterol from tissues
VLDL function
deliver triglycerides to tissues from liver
chylomicron function
deliver triglyceride from intestine to liver
What is the cofactor for LPL
C-11
LPL function
break down triglycerides in VLDL and chylomicron to deliver FA to tissues
remaining glycerol returns to the liver
Where is LPL located
in capillary beds
What 3 enzymes are associated with reverse transport / HDL?
LCAT
CETP
SR-B1
LCAT function
makes cholesterol ester so it can get into neutral core for transport by HDL
cholesterol is now able to be transported back to the liver
CETP function
move cholesterol ester from HDL to other lipoproteins
how is cholesterol created from VLDL?
CETP moves cholesterol ester from HDL to LDL
SR-B1 function
scavenger receptor directly transports cholesterol and ester to tissue or liver
tissues that commonly require cholesterol express what receptor
SR-B1
what tissues commonly require cholesterol?
adrenal cortex and sex organs
need cholesterol to produce hormones
What binds to the LDL receptor?
the C-terminal of Apo B-100
How do chylomicrons bypass the liver?
move through the lymph first and then the blood
bile acids
break down dietary fat and cholesterol to package into chylomicrons
what is elevated in familial hypercholesterolemia?
LDL levels
familial hypercholesterolemia genetic pattern
autosomal dominant / haploinsufficiency
what form of familial hypercholesterolemia is most severe?
homozygous
xanthuma
cutaneous deposit of cholesterol that can be seen in familial hypercholesterolemia
statin MOA
block cholesterol production by blocking HMG CoA Reductase
what causes familial hypercholesterolemia?
mutations in LDL receptor gene
by mutating the LDLR, you are unable to uptake LDL which is a bad thing
no uptake also indicates to liver artifically low LDL levels and liver will produce more cholesterol (even though levels in blood are high)
PCSK-9 function
determines if LDL receptor will be degraded or re-expressed on the membrane
PCSK-9 prefers degrading the receptor
PCSK-9 inhibitor
by inhibiting PCSK-9, we recycle more LDL receptors which is good for lowering serum LDL
Where does most serum cholesterol come from?
de novo synthesis in liver
this is why statins work better than exercise in lowering cholesterol
what are LDL and remanent receptors coated with?
clathrin
