Lipid Transport Flashcards
What are the 3 interlinked pathways in which lipids are transported?
The exogenous pathway transports lipid from the gut to the liver
The endogenous pathway transports lipids synthesised by the liver to non-hepatic tissue including adipocytes
Third pathway takes lipid from the circulation and from non-hepatic tissue back to the liver for further metabolism
What are lipoproteins?
FA are transported around the body as lipoproteins. 5 types of lipoprotein:
Chylomicrons
Very low density lipoproteins (VLDL)
Intermediate density lipoprotein (IDL)
Low density lipoproteins (LDL)
High density lipoproteins (HDL)
Each lipoprotein particle has a diff function
Draw the structure of a lipoprotein
Describe key differences in the composition of VLDL, LDL and HDL
Draw a table to describe the protein composition of the different lipoproteins
VLDL made in the liver is released with only B100. As it circulates it acquires Apo C and E from HDL
What is the function of apolipoproteins/apoproteins
Functions are:
- structural- help form the particle
- to solubilise lipids
- Act as enzymes or enzyme cofactors: eg Apo CII is a cofactor for lipoprotein lipase
- Tissue targeting: Apo B100 and E bind to the LDL receptor. Apo E binds to the HDL receptor
What happens to dietary lipids once consumed?
Dietary lipids enter the gut as TG
These will undergo breakdown using lipases to form FA and glycerols. These will enter into the cell and reform TG
These TG are combined with ApoB48 to form chylomicrons. The mature chylomicrons are then released into the lymphatic system, then enter the circulation via the thoracic duct.
What are chylomicrons?
Reflects meal composition
• Chylomicrons are very low density due to a proportionally high triglyceride composition
• Also contain fat soluble vitamins A and E
• Chylomicrons have a long half-life in the circulation (~1 hour), which is longer than TGs alone.
• Remnants removed by the liver w involvement of Apo E
What are VLDLs? How are they made and removed?
Made by the liver when carb intake exceeds immediate needs
VLDLs are first made w just ApoB100. Later, they get ApoC2 and ApoE from HDLs to become mature. Formation stimulated by insulin and inhibited by glucagon
Remnants removed by the liver by apoE. VLDL lipid uptake is initiated through the binding of ApoB100 to the LDL receptor
When the LDL receptor becomes saturated a low affinity scavenger receptor is activated to remove any excess VLDL
What are LDLs?
Are the major carrier of cholesterol
Metabolised slowly - 3 days
Carry cholesterol to the periphery and regulate de novo synthesis= regulate cholesterol anabolism
Contain 1 ApoB100 which can bind to a specific receptor on hepatocytes
Describe HDLs
Can be created in 3 ways: As nascent particles by the liver and intestine. Budding of apolipoproteins from chylomicrons. From free ApoAI
The functional role of HDL is to remove plasma cholesterol. The LCAT enzyme esterifies cholesterol, preventing it from returning to the cell
Particularly important in vascular cells – prevents foam cell formation
Cholesterol rich HDL can either deliver it to the liver or exchange it w other particles inc VLDL
HDLs also deliver cholesterol to tissues such as the testis and adrenal
What is the clinical significance of HDL vs LDL cholesterol?
Describe Receptor-Mediated Endocytosis of lipoproteins
Lipoproteins like LDLs are removed from circulation via receptor-mediated endocytosis
- ApoB100 on the LDL binds to the LDL receptor on the cell membrane
- The binding initiates endocytosis, taking the LDL into the cell in an endosome.
- The endosome fuses with a lysosome. Enzymes are released, hydrolysing the LDL to fatty acids, cholesterol and amino acids
- The cholesterol is esterified by LCAT
Within the cell, the enzyme HMG-CoA reductase synthesises cholesterol, this is inhibited by high intracellular cholesterol levels and statins.
What are scavenger receptors?
Scavenger receptors are low affinity receptors found on endothelial cells + macrophages
If circulating LDL levels rise and aren’t regulated, specific, high-affinity receptors ya no pueden removerlos– this is where scavenger receptors remove excess LDL
BUT scavenger receptors are unregulated, this means that they will keep taking up mas y mas lipid, filling endothelial cells and macrophages w cholesterol to form foam cells.
