Wk 1 Lipid Transport Flashcards
What are key functional components of lipoproteins?
ApoA = alpha lipoprotein
ApoB = beta lipoprotein
What are the lipoproteins associated with?
ApoA - HDL
ApoB - chylomicrons, VLDL, IDL, & LDL
What are the two forms of ApoB?
- ApoB-48: synthesized in intestines, found on chylomicrons
- ApoB-100 (contains extension to ApoB-48, making it heavier), in liver
Both act as markers for the different lipoprotein carriers
What are the 3 lipid transport pathways?
- Delivery of dietary lipids to adipocytes and hepatocytes
- Delivery of de novo synthesized lipids to adipocytes and other cells
- Transport of HDL particles
How are dietary lipids transported to adipocytes and hepatocytes?
- food broken down to FFA & free cholesterol & absorbed by enterocyte
- enterocyte esterifies & packages FA (as TAG) & cholesterol (as CE) catalyzed by MTP (microsomal triglyceride protein) w/ ApoB-48 to make “nascent” chylomicrons that travel in the lymphatics
- nascent chylomicrons undergo maturation in bloodstream, pick up ApoE and ApoCII to make HDL
What is a makes a chylomicron mature?
Has ApoB-48. ApoCII, and ApoE
Role of ApoCII
Cofactor for lipoprotein lipase (LPL)
LPL role
Breakdown TAG from chylomicron into FFAs
What happens to FFA after they’re broken down by LPL in capillaries?
Transferred into adipocyte for storage
What happens to cholesterol in chylomicron?
Stays in chylomicron with ApoE after FFA dropped at adipocyte.
ApoE receptors on hepatocytes recognize and endocytose the cholesterol
What happens to ApoCII after FFAs delivered to adipocytes?
It is transferred to circulating HDL
What is the pathway for de novo synthesized cholesterol from the liver?
- In hepatocytes, TAG + CE + ApoB-100 packaged w/ MTP (microsomal triglyceride protein) to make nascent VLDL
- VLDL enters bloodstream, picks up ApoCII and ApoE from HDL to form mature VLDL
- VLDL encouters LPL (lipoprotein lipase) in capillaries near adipocytes w/ ApoCII acting as cofactor
- LPL breaks down TAG in VLDL
- ApoCII returns to circulating HDL
- VLDL is now IDL
- ApoE receptor on hepatocytes recognizes IDL, endocytoses it, degrades TGs w/ hepatic lipase
- LDL is exocytosed
What is different about HDL transport?
Transports lipids from other cells/tissues throughout body to the liver.
So, when HDL is made in enterocytes or hepatocytes (nascent), it is lipid-poor
Where is ApoA synthesized and what is it associated with?
hepatocytes and enterocytes
associated w/ HDL
How do HDL particles made by enterocytes get ApoE and ApoCII?
From HDL particles in the bloodstream that were made by hepatocytes
What specifically does HDL pick up?
TAGs from around body and NEFAs from macrophages
What is lecithin-cholesterol acyltransferase (LCT)?
An enzyme in HDL that catalyzes esterification of cholesterol to cholesterol esters and thus forming the mature HDL
What is the biggest reservoir of cholesterol?
Liver
Role of HMG-CoA reductase
- RLE during intermediate step in cholesterol synthesis from acetly-CoA to cholesterol
- amount and activity regulates amount of cholesterol biosynthesis
Role of SREBP
= sterol-response element binding protein
1. a transcription factor that regulates all cholesterol synthesis genes
2. low cholesterol -> increased SREBP -> increases HMG CoA reductase -> increases cholesterol synthesis
3. regulates levels of LDLR
How do statins function to reduce LDL?
They are competitive inhibitors of HMG-CoA reductase and therefore block cholesterol synthesis and decrease intracellular cholesterol levels.
-> reduced intracelluar levels activate and increase SREBP, which increases transcription of LDLR, which pulls LDL from circulation
Statins can reduce circulating LDL levels up to 60%
2 ways a cell obtains cholesterol
- biosynthesis - almost all human cells can synthesize cholesterol
- Uptake circulating cholesterol - obtained from diet or after synthesis by other cells
Where is the LDLR (receptor) found?
On hepatocytes, which take up LDL from the circulation into cells
What does the LDLR bind to?
ApoB-100 on the LDL
