Lipoprotein metabolism Flashcards
four main classes of lipids. Which are hydrophobic?
Free Fatty Acids, Triglycerides (hydrophobic), Phospholipids, cholesterol (cholesteryl ester is hydrophobic)
HMG-CoA Reductase
Rate limiting step in synthesis of cholesterol in the liver
describe the structure of a typical lipoprotein
apolipoproteins, amphipathic surface, hydrophobic core (triglycerides and cholesteryl ester)
Four major pathways of lipoprotein transport
Exogenous, endogenous, Reverse cholesterol transport, enterohepatic circulation
LPL
lipoprotein lipase; converts triglycerides to FFA’s
LCAT
lecithin-cholesterol acyltransferase; transfers acyl group to cholesterol. Important in ApoA1>pre-beta>spherical HDL
CETP
cholesterol ester transfer protein; transfers cholesterol and cholesteryl ester to LDL for delivery to liver
lipoproteins by density (and size)
HDL3, HDL2, LDL, IDL, VLDL, chylomicron remnant, chylomicron
progression to LDL
VLDL->IDL->LDL
progression to HDL
Prebeta->HDL3->HDL2
exogenous pathway
chylomicrons are taken up by gut, packaged by enterocytes and delivered to liver. Maturation of nascent chylomicrons happens when ApoC and ApoE are picked up from HDL. ApoC is then the cofactor for LPL which then leaves a chylomicron remnant
endogenous pathway
Nascent VLDL produced by liver pick up Apo C and ApoE from HDL to form VLDL. ApoC with LPL makes FFA’s and you get IDL. This is converted to LDL and can go to liver or endothelial cells via LDLR
Reverse Cholesterol Transport
From macrophages to liver for excretion in bile. ApoA1 incorporated into preBeta HDL then LCAT makes it into HDL3. Then matures by exchanges with chylomicrons,vldl to become HDL2 which can be delivered directly to liver via SRb1 or converted by CETP to LDL.
enterohepatic circulation
recirculation of bile salts in the gut
familial hypercholesterolemia
Autosomal dominant mutation in LDLR. Heterozygoes have cholesterol ~250, homozygotes ~1000
