Lipoproteins Flashcards
What are the three pathways of lipoprotein transport?
Exogenous
Endogenous
Reverse cholesterol transport
What is a lipoprotein?
a particle for transporting lipids
Where are lipoproteins made?
in the liver and intestine
What are the types of lipoproteins and where are they made?
Chylomicron (intestine)
LDL, IDL (liver)
VLDL, HDL (liver, also little from intestine)
What is the composition of a lipoprotein?
non-polar lipids within: TGs, cholesteryl ester
polar lipids on the outside: phospholipids, free cholesterol, apoproteins
What is does an apoprotein do?
plays role in assembly, secretion, metabolism, and clearance, associated with lipoproteins
What are the major apoproteins in lipoprotein metabolism?
B; A-I; A-IV; C-II; E
What does ApoB do?
48 and 100 are packaged with chylomicrons and VLDLs respectively
What’s the difference between ApoB-48 and ApoB-100?
48 is shorter because it lacks the LDL binding sequence; associated with chylomicrons and intestinal cells; 100 associated with VLDL and hepatocytes
What are the 2 main roles of ApoA-I?
HDL apoprotein component, and cofactor for LCAT
What is LCAT?
Lecithin:cholesterol transferase; functions to pick up and esterify free cholesterol for internalization to the lipoprotein core
What is ApoA-IV?
produced in intestine and bound to chylomicrons; functions to activate LCAT and a bunch of other things as well; also the only apoprotein that also exists as free protein in blood plasma
What is the main role of ApoC-II?
to bind and activate LPL for uptake of TGs; located in chylomicrons, VLDL, and HDL
What does ApoE do?
it’s the ligand in remnant chylomicrons for hepatic LDL receptors, along with ApoB-100
What is the name of the enzyme complex that edits ApoB mRNA?
ApoB EC 1
What kind of post-transcriptional modifications does the ApoB mRNA undergo?
to make ApoB-100: nothing
to make ApoB-48: one base is changed to make an earlier stop codon
What does LPL do and where is it located?
it hydrolyzes the TGs within lipoproteins that have ApoC-II; located in capillary endothelial cells
What does HL do and where is it located?
hepatic lipase will play a role in remnant lipoprotein uptake to the liver, independent of LDL receptors, as it’s located on proteoglycans on hepatocytes
What does LCAT do and where is it located?
it esterifies free cholesterol for internalization to HDL in the reverse cholesterol transport path; located in HDL
What does ETP do and where is it located?
ester transfer proteins catalyze exchange of lipids between LDL and HDL; located there
What does the ABC class of proteins do and where are they located?
they mediate the lipid efflux from peripheral cells to HDL for return to liver, as well as help form nascent HDLs
What’s the difference between ABC proteins A1 and G1?
A1 works with more nascent HDLs and G1 works with more mature HDLs
What does HMG-CoA reductase do, and where is it located?
it’s the rate-limiting enzyme in cholesterol synthesis
What does ACAT do, and where is it located?
catalyzes the conversion of free cholesterol to cholesterylester within cells for storage
What is the function of the LDL receptor and where is it located?
binds ApoB-100 and ApoE (less affinity) for hepatic uptake of LDLs and remnant lipoproteins; located in liver cells
What does a defect in the LDL receptor cause?
familial hypercholesterolemia, HLD; atherogenic
What is LRP?
LDL Receptor Related Protein: functions in hepatic uptake of remnant lipoproteins
What is SR-B1?
scavenger receptor B1; mediates hepatic uptake of cholesteryl ester from HDLs
What is the final step in the HDL/reverse cholesterol transport pathway?
uptake of HDL into the liver, as mediated by SR-B1
What are the overall steps of lipoprotein trafficking, starting from the liver?
VLDL secreted; gives away TGs to peripheral tissue; remnant becomes IDL then LDL; LDL remnant reuptaken by the liver’s LDL receptors
What are the overall steps of lipoprotein trafficking, starting from the intestine?
chylomicron secreted; gives away TGs to peripheral tissue; remnant reuptaken by the liver by
What are the overall steps of the reverse cholesterol transport system?
HDL secreted from the liver or gut with no contents; picks up free cholesterol from peripheral tissues; esterifies/internalizes it with LCAT; SR-B1 transports it into the liver
How does a cholesterol get from intestine to liver?
HDL or chylomicron
How does a cholesterol get from liver to peripheral tissue?
VLDL
How does a cholesterol get from adipocyte to the liver?
HDL
What does a defect in the LDL receptor cause?
familial hypercholesterolemia, HLD; atherogenic
What is LRP?
LDL Receptor Related Protein: functions in hepatic uptake of remnant lipoproteins
What is MTP (microsomal triglyceride transfer protein)?
a heterodimeric protein in the ER membrane that lipidates ApoB (large subunit does) so it can be added to the TG to make the primordial chylomicron; functions to lipidate proteins using lipids from ER memebrane
What is the final step in the HDL/reverse cholesterol transport pathway?
uptake of HDL into the liver, as mediated by SR-B1
What are the overall steps of lipoprotein trafficking, starting from the liver?
VLDL secreted; gives away TGs to peripheral tissue; remnant becomes IDL then LDL; LDL remnant reuptaken by the liver?
When are phospholipids removed from the chylomicron/lipoprotein?
whenever they become excessive after the lipoprotein gives away its content
What are the overall steps of the reverse cholesterol transport system?
HDL secreted from the liver or gut with no contents; picks up free cholesterol from peripheral tissues; esterifies/internalizes it with LCAT; SR-B1 transports it into the liver
What regulates the amount of ApoB in lipoproteins?
MTP - because if MTP doesn’t lipidate it then the ApoB gets degraded
How does a cholesterol get from liver to peripheral tissue?
VLDL
How does a cholesterol get from adipocyte to the liver?
HDL
How are TGs from the diet processed to get to the circulation?
take up into enterocyte as FA and MAG; reassembled into TG in ER, packaged with ApoB-48 and A-IV; buds off and travels to golgi independent of MTs as a primordial chylomicron; in golgi gets more proteins added; buds off and secreted into circulation as chylomicron
What proteins are in the ER to reassemble the FA and MAG?
MGAT and DGAT
What is MTP?
a protein in the ER membrane that helps add ApoB to the TG to make the primordial chylomicron
By what process does a chylomicron pick up Apo E and C-II?
transfer from HDL particles it encounters in circulation
When is ApoB-48 removed from the lipoprotein?
never
when are phospholipids removed from the chylomicron/lipoprotein?
whenever they become excessive after the lipoprotein gives away its content
What subunit of MTP has solubility responsibility?
the protein disulfide isomerase; maintains solubulity of the large subunit