Cholesterol• exogenous (dietary) cholesterol delivered to

liver via chylomicron remnants.• endogenous cholesterol synthesized primarily

in the liver from AcCoA (extrahepatic tissues also synthesize cholesterol)

• in the liver, cholesterol is either converted to bile salts or to cholesterol esters and packaged into VLDLs.

• Peripheral tissues obtain most of their exogenouscholesterol from LDLs and convert it back tocholesterol for use in membranes or store incholesterol ester droplets.

• LDLs deliver cholsterol to the tissues - HDLscirculate it back to the liver.

• Excess cholesterol is disposed of by the liver asbile salts.

Lipoproteins-1• hydrophobic core (TAGS, cholesterol esters)• hydrophilic surface (P-lipids, cholesterol, and

apolipoproteins)

• Functiontransport of lipids in blood

• Types of lipoproteins(classified according to density)

• chylomicron• very low density (VLDL)• intermediate density (IDL)• low density (LDL)• high density (HDL)

Protein content increase, lipid decreases as density increases.

% TAGS

% Protein

Chylomicron VLDL IDL LDL HDL

85%

2%

8%

33%

Lipoproteins-2• Chylomicron:

• 85% TAG, 4% chol., 8% protein• 80 -500nm•formed in intestinal epithelial cells• deliver exogenous TAGS to tissue• ApoCII activates lipases in capillary cell

walls releasing FFA to tissue• chylomicron remnants return to liver where

they bind to ApoE receptor and are taken up• 1/2 life in blood - 4-5 minutes

• VLDL:• 50% TAGs, 22% choles., 10% protein• 30 -100 nm • formed in liver• deliver endogenous lipids to other tissues

(mainly muscle and fat cells)• ApoCII activates lipases in capillary cell

walls releasing FFA to tissue• converted to IDLs and LDL as lipids are

released

• IDL: (31% TAGs, 29% choles., 18% protein) • formed from VLDLs as lipids removed• some IDLs return to liver• rest converted to LDLs by further removal

of lipids

Lipoproteins-3

• LDL: “bad” cholesterol• 10% TAGs, 45% choles., 25% protein• 25 - 30 nm• formed as lipids removed from VLDLs

and IDLs. • all Apolipoproteins lost except ApoB100• bind to LDL receptor via ApoB100 and

taken up by endocytosis by hepatic and other tissues (50-75% taken up by liver). Primary mode of cholesterol delivery to tissues.

• Synthesis of LDL receptor is inhibited byhigh levels of intracellular cholesterol and stimulated by low levels of cholesterol.Therefore, cholesterol uptake is closly matched to intracellular cholesterol levels.

• HDL: “good” cholesterol• 8% TAGs, 30% choles., 33% protein• 7.5 - 10 nm• formed in liver• scanvenge cholesterol from cell surfaces

and other lipoproteins and deliver it to liver.• Convert cholesterol to cholesterol ester• bind to “scanvenger receptor” on liver cell

surface - cholesterol esters taken up and HDLs released and reenter circulation.

Lipoproteins-4