MMT: lipoprotein metabolism Flashcards
What is the exogenous lipoprotein?
Chylomicrons
Once chylomicrons donate their TGs, where do they go?
Back to the liver
What is the endogenous lipoprotein?
VLDL
What happens to VLDL remnants?
They return to the liver as LDL or deposit in extrahepatic tissues as LDL
Which lipoprotein is involved in reverse cholesterol transport?
HDL
Arrange lipoproteins in terms of size (large to small).
- Chylomicrons
- VLDL
- IDL
- LDL
- HDL
The density of lipoproteins is largely due to…
Protein; high density have the most protein and least TGs
What does ApoA-I do?
Activates LCAT that helps but cholesterol into HDL
Where is ApoA-I found?
HDL
Where is ApoA-II found?
HDL
Where is ApoA IV found?
Chylomicrons and HDL
Where is ApoB-48 found?
Chylomicrons
Where is ApoB-100 found?
VLDL and LDL
Where is ApoC-I found?
VLDL and HDL
Where is ApoC-II found?
Chylomicrons, VLDL, HDL
Where is ApoC-III found?
Chylomicrons, VLDL, HDL
What does ApoC-III do?
Inhibits LPL
Where is ApoD found?
HDL
Where is ApoE found?
Chylomicrons, VLDL, HDL
What does ApoE do?
Trigger clearance of VLDL and chylomicron remnants
Which apolipoprotein is associated with Abetalipoproteinemia?
ApoB
Where does chylomicron acquire ApoE and ApoC-II?
HDL
Where is VLDL synthesized?
Liver
What does VLDL do?
Transport TGs and cholesterol from the liver to other tissues
How does VLDL acquire ApoC-II and ApoE?
From HDL
What is abetalipoproteinemia?
A condition caused by MTP defect that results in ApoB proteins not being released from ER and added to chylomicrons and VLDL
What are symptoms of abetalipoproteinemia?
Lipid malabsorption, caloric deficiency, lipid soluble vitamin deficiency
What is lost in the conversion of VLDL to IDL?
ApoC-II
Hepatic lipase can interact with…? What is lost in this process?
IDL; ApoE
Describe the life cycle of LDL.
- ApoB-100 on LDL interacts with LDLR on hepatocyte or peripheral tissue
- LDL is endocytosed and put in an endosome, where it separates from the LDLR
- LDL combines with a lysosome, and it is degraded
- Cholesterol is deposited in tissue
- Receptor is recycled
In hepatocytes, what regulates degradation of LDLR?
PCSK9
How does PCSK9 work?
It binds to the receptor and causes it to stay in the endosome after endocytosis, causing it to be degraded as opposed to recycled
What is SREBP?
A transcription factor for lipids
What is Lp(a)?
A lipoprotein that can bind to ApoB-100 and increase risk of cardiovascular disease
What lipoprotein is involved in reverse cholesterol transport?
HDL
Nascent HDL originates from…
Liver and small intestine
What proteins are found on HDL?
ApoA-I, ApoC-II, ApoE, LCAT, and ABCA1
What does LCAT do?
Convert cholesterol to cholesterol esters to pack them into HDL
What activates LCAT?
ApoA-I
What receptor allows cholesterol to be transferred into hepatocytes?
SR-B1
What is CETP?
Transfers lipids from HDL to VLDL
Type I hyperlipidemia: cause, what is in excess?
Cause: LPL or ApoC-II deficiency
Excess: chylomicrons
Type IIa hyperlipidemia: cause, what is in excess?
Cause: LDL receptor deficiency or ApoB100 defect
Excess: LDL
Type IIb hyperlipidemia: cause, what is in excess?
Cause: decreased LDL receptor or increased ApoB-100
Excess: LDL and VLDL
Type III hyperlipidemia: cause, what is in excess?
Cause: ApoE deficiency
Excess: chylomicron remnants and IDL
Type IV hyperlipidemia: cause, what is in excess?
Overproduction of VLDL
Excess: VLDL
Type V hyperlipidemia: cause, what is in excess?
Cause: increased VLDL production and decreased LPL
Excess: chylomicrons and VLDL
A patient has pancreatitis, cloudy plasma with a creamy top layer, hepatosplenomegaly, and eruptive xanthomas. What familial hyperlipidemia do they have?
Type I
How do we diagnose type I hyperlipidemia?
TG count
A patient has tendinous xanthomas and atherosclerosis. What hyperlipidemia do they have?
Type IIa
A patient has palmar xanthomas and tuberoeruptive xanthoma. What familial hyperlipidemia do they have?
Type III
