Lipoprotein Assembly Flashcards
apoB
ApoB is the main protein on CM, VLDL, and LDL
ApoB100 vs apoB48
ApoB100: stabilizes VLDL and LDL, produced in liver and present on VLDL and LDL
1. structural protein
2. LDL uptake, recognized by LDL receptor
ApoB48: N-terminal of ApoB100, 48% of ApoB100, cannot bind to LDL because it has no C-terminal, on VLDL/chylomicron remnants is recognized by the remnant
1. Structural protein
2. not recognized by LDL receptor
How is ApoB48 produced
Transcribed from the same gene as apoB100, but under goes RNA editing in the intestine
Where are Cm/VLDL assembled? structures of CM,VLDL,LDL
CM in intestine
VLDL in liver
CM/VLDL:
* Particles composed of a TG-rich core with a small content of CE, a surface monolayer of phospholipid and cholesterol and
apolipoproteins
* Although CM and VLDL are produced by different tissues, the
process is similar
LDL: Produced in circulation from VLDL, CE-rich core
5 steps
model of VLDL/CM assembly? does it require co-translational or post-translational lipidation?
Required co-translation and post-translational lipidation
1. Generation of lumenal lipid droplets
2.Translation/ translocation of apoB into ER lumen
* Co-translational addition of lipids to apoB –> nascent CM/VLDL
3. Post-translational addition of lipids (fusion) to nascent CM/VLDL –> mature CM/VLDL
* apoB is fully translocated
4. Secretion into circulation
5. Addition of other apolipoproteins (apoE, apoCII) occurs in the circulation
What protein is needed for VLDL/CM assembly
MTP
Facilitates the formation of CM/CLDL by catalyzing the transfer of TG and PL
Abetalipoproteinemia (description, mutation in what protein, symptoms, treatment)
Genetic disease of lipoprotein assembly (CM/CLDL)
Mutation in MTP
absence of apoB-containing plasma lipoproteins (CM, VLDL, and LDL)
low concentration of TG and cholesterol in blood
Failure to grow in infancy
fatty stools
loss of vision
vitamin E deficiency
Low fat diet, vitamin E supplement
MTP inhibitor
Cholesterol is reduced, has some toxic effects
Increased ALT indicates liver damage
also caused fatty liver
What does increased ALT indicate
Indicates liver damage
MTP function
Facilitates the formation of CM/CLDL by catalyzing the transfer of TG and PL