Lipids (Lecture 21) Flashcards
where is ApoB48 found?
coating the chylomicron
what is orlsitat
inhibitor or pancreatic lipase
what is olestra
prevents the uptake of lipids int the enterocytes and into the blood.
what’s the issue with inhibiting lipids uptake into enterocytes?
this causes cyatorrhea (diarrhea with lipids)
what is the general structure of a lipoprotein?
must package neutral lipids (unchanged core)
- cholesteryl ester
- tryglycerides
charged exterior to interact with the aqueous environment
- apolipoprotein
- free cholesterol
- phospholipids
what are lipoproteins?
circulating lipid carrier composed of a n neutral lipid core, a monolayer of polar surface lipids and at least one apolipoprotein
what are apolipoproteins?
apolipoproteins are amphipathic proteins that insert in lipoproteins and serve as ligands for lipoprpotein recognition and docking.
explain the exogenous pathways for the metabolism of lipoproteins
dietary lipids are solubilized in the small intestine with bile salts
taken up by enterocytes
chylomicrons are generated and secreted into the blood (recall that chylomicrons contain ApoC ApoE and ApoB48)
the chylomicrons will circulate into the blood and when they encounter the capillaries, they encounter LPL which will digest the triglycerides within the chylomicron to take up free FAs into the muscle/adipose
chylomicron remnants iOS what is left after the depositing of fatty acids. these remnants are poor in triglycerols have more cholesterol
the chylomicron remnant will bind to the LRP (ligand being apob48) and the LDLR (apoe ligand)
the liver will take up the remaining triglycerides, cholesterol and remaining cholesterol esters
what is the cofactor that a activates lipoprotein lipase?
ApoC II (on surface of chylomicrons)
explain the endogenous pathway for the metabolism of lipoproteins
once the VLDL are secreted from the liver, they circulate carrying triglycerides and cholesterol esters into the blood until they can deliver this content to muscle/adipose via LPL.
recall that the required cofactor for LPL is apoc
this is how energy is transferred from the liver to the muscle or for storage, to the adipose tissue
after unleashing their intracellular neutral lipids, IDL is produced and there is more cholesterol ester.
the IDL are taken up by the LDLR (apoe/apob100) of the liver
hepatic lipase on the liver will get rid of all of IDL’s remaining triglycerides, thus its taken up by the liver. this produces LDL (apob100)
LDL will then deliver cholesterol ester to peripheral tissues when in need of cholesterol
why do tissues (peripheral) need cholesterol?
membrane synthesis (cell division)
tissues generating hormones derived from cholesterol
what are the two fates of the LDL?
taken up by the liver
delivered to the peripheral tissues that need cholesterol (efficient, since synthesizing cholesterol de novo is very costly)
what occurs when cholesterol is taken up by the LDLR?
endocytosis:
the LDL bind to the ApoB receptors of the cell.
clathrin coated pit will form invaginations until a vesicle is formed.
the vesicle will undergo the endosomal pathway and it’ll be acidified in order to be digested via the lysosome. while the receptor is recycled.
cholesterol esters and re-esterified to make lipid droplets
(free cholesterol could be mixed with the de novo pool of cholesterol )
what it the purpose of HDL?
take cholesterol and triglycerides from various tissues when they are in excess. this will be carried to the liver
what is the reverse cholesterol transport?
takes excess cholesterol from peripheral tissues will br efflux onto a lipid-free ApoA-1.
ApoA-1 will acquire cholesterol and PL and will then generate some nascent lipo -particle (pre HDL)
the cholesterol is transferred via ABCA1 to the ApoA 1
in the plasma, there’s an esterification of cholesterol via LCAT.
the cholesterol found on the surface of the pre HDL is now esterified and found on the inside of the HDL molecule.
another LCAT esterification occurs
an exchange of TAG and cholesterol ester occurs between the HDL and the VLDL
the mature particles doc to the surface of the liver, to a receptor called SRB1. this will return the cholesterol/TAG are transported into the liver
