lipids/cholesterol Flashcards
describe Hormone-sensitive Lipase (HSL)
- Found on adipose cell surface
- Release free fatty acids into blood that bind to albumin
- HSL is INHIBITED by INSULIN
define lipoproteins
- synthesized in well-fed state for the sole purpose of transporting lipids
- Archetecture
- inside is very hydrophobic molecules (cholesteryl esters)
- surrounding hydrophobic core we have anti polar membrane
- on the surface you have hydrophilic head groups of cholesterol
–> proteins on the surface provide structure and contain enzymes to allow the transport of lipids into and out of the lipoprotein molecules (entery and exit)
define chylomicrons
- transport of dietary lipids
- very large, synthesized in enterocytes, made for transport of consumed lipids
Define very-low density lipoproteins
- for transport of endogenous lipids
- made for the transport of liver generated lipids
High density lipoproteins (HDL)
- reverse lipid transport/excretion
- made empty, and as they circulate they suck up lipids from the lipid membranes
Apo A
- activators of lecitin: cholesterol acyltransferase (LCAT)
–> makes cholesterol very hdyrophobic and therefore trapping them into the core
–> extract lipids from membranes for reverse transport
Apo B
- Structural proteins, interact with lipoproteins receptors and mediate the uptake of the particle into target cell
–> scaffold to give shape and also helps the molecule interact with receptors
Apo C
- Modulate lipoprotein lipase (LPL/HTGL) activity
–> LPL liberates free fatty acids and glycerol from lipoproteins
–> facilitates the EXIT of lipids from lipoproteins
Apo E
- bind to receptors to allow removal of remnant particles from the circulation
- Allow the interaction of lipoproteins with receptors
Describe the formation of Chylomicron
- In order to take up lipids (TG) from the diet you need to break them down via PANCREATIC lipase (TG –> MG +FA) and absorbed into enterocytes
- Once in enterocytes MG + FA form TG and are formed into Chylomicron with Apo B-48
- As it goes through circulation it collect Apo E and Apo C from HDL particles
- Apo C activates lipoprotein lipase (LPL) and release Free fatty acids and glycerol
- As chylomicron shrink with the release of more lipids it forms a remnant and is recycled in the hepatocyte
describe endogenous lipid production
- the hepatocyte combine cholesterol and Apo B100 to form VLDL
- VLDL leaves hepatocyte and enters circulation (still in immature state, does nto have function proteins)
- Collects Apo C and Apo E from HDL particles
- Apo C activates lipoprotein lipase (LPL) and releases FA + glycerol into muscle and storage
- Becomes heavier as it releases lipids (VLDL –> IDL –> LDL)
describe the role of LDL
- Two options:
- LDL binds to hepatocytes
–> becomes treated in endolysosome and degraded
–> should NOT be a lot of LDL in circulation
–> functional of how much energy is in liver (leads to accumulation)
- LDL binds to pretty much every other cell type
–> In Macrophages, LDL become internalized and if they are faced with lots of LDL (oxygenized LDL) they take up a lot of it!!
–> filled with oxygenated LDL they can start forming atherosclerosis and plaques
describe the reverse cholesterol transport
- Liver makes Nasc. HDL with triacylglycerol, Apo E, Apo C and Apo A
- as it circulates, HDL particles pick up lipids from peripheral cells by interactions between ABCA1 and Apo A
- Once cholesterol is picked up, LCAT makes sure cholesterol stays on the inside of the cell by conversion to cholesteryl ester
- HDL transfer cholesteryl esters to VLDL via CETP (mech for making VLDL rich in cholesterol
- ONCE HDL is full it binds to scavenger receptor BI and the hepatic lipase removes cholesteryl esters from it and is converted to bile sates and excreted.
Elevated cholesterol, normal triglycerides
- Familial hypercholesterolemia (FH)
–> results from defects in the Apo E/B (LDL) receptor
–> autosomal co-dominant trait
- Familial defective ApoB100 (FDB)
–> similar to FH
–> defective apoB100 prevents binding of LDL to receptor
Elevated triglycerides
- Familial combined hyperlipidemia (FCHL)
–> variable etiology; may result from:
–> overproduction of Apo B100 or..
–> increased production of VLDL, abundance of VLDL, IDL, LDL
- Familial dysbetalipoproteinemia (FDBL)
–>defective ApoE prevents uptake of remnants by liver
–> increase in all Apo B-containing lipoproteins
