1. Lipoproteins The serum lipoproteins are complexes of lipids and specific proteins called "apoproteins". Functions of Lipoproteins Help to transport lipids in blood. Since lipids are water insoluble, they can't be transported in blood. For their transport, they are conjugated with apoprotiens forming lipoproteins which are water soluble and can be transported in blood Composition of lipoproteins: Lipoproteins are composed of a neutral lipid core (TAG and cholesterol ester) surrounded by a shell of apoproteins, phospholipids and free cholesterol, all oriented so that their polar proteins are exposed to the surface of lipoprotein, thus making the particle soluble in aqueous solution.

2. Lipoprotein Structure Spherical molecules of lipids and proteins (apoproteins) = amphipathic molecules Outer coat: - Apoproteins - Phospholipids - Cholesterol ( Unesterified ) Inner core: - TAG - Cholesterol ester (CE)

3. Apoproteins There are five major classes ( from A-E) of apoproteins –divided by structure & function –Each class has subclasses e.g. Apo A1, Apo CII –Functions of apoproteins Some are required as structural proteins e.g.B48, B100 Some are activators, e.g. Apo CII Some are recognition sites (recognized by the receptors and help binding of lipoprotein to its receptors on cell surface e.g. Apo E and Apo B

4. Types of Lipoproteins There are various types of lipoproteins: –They differ in lipid and protein composition, therefore they differ in: Size, density and apoprotein content They are: Chylomicrons (CM) Very low density Lipoprotein VLDL) Low density Lipoprotein (LDL) High density Lipoprotein (HDL)

5. Chylomicrons (CM): Synthesis: CM is synthesized in intestinal mucosal cells from dietary TAG, cholesterol ester, phospholipids and apoprotein B48. -Apoprotein B-48 is the structural apoprotein that is unique to CM and synthesized in endoplasmic reticulum. -Function: CM carries dietary (exogenous) TAG and CE from intestinal mucosal to blood

6. Metabolism of CM -Nascent chylomicrons (TAG, CE, B48) travel through the lymph into the blood. - Apo CII, the activator of lipoprotein lipase (LPL), and apo E are transferred from HDL, and mature chylomicrons are formed. -TAG is hydrolysed by the activated LPL into glycerol (which move to liver) and free fatty acids which are carried by albumin to either adipose tissue (to be stored) or to muscles (to be used as source for energy). - The chylomicron remnants interact with receptors on liver cells (which are recognized by apo E) and are taken up by endocytosis. The contents are degraded by lysosomal enzymes, and the product (amino acids, fatty acids, glycerol, cholesterol, and phosphate) are released into the cytosol.

8. CM metabolism

10. VLDL: Synthesis: VLDL is synthesized in the liver. It contains apoprotein (apo B- 100) as structural apoprotein. Function: VLDL transport endogenous lipids (synthesized TAG and CE) and dietary CE from liver to blood. -In blood, Apo CII and Apo E are transferred from HDL. -Apo CII activates LPL which hydrolyses TAG into glycerol and free fatty acids. VLDL is converted into VLDL reminant then to LDL.

12. LDL - synthesis: LDL is produced in the circulation as the end product of VLDLs Function: LDL transport mainly cholesterol ester from blood to peripheral tissues that require cholesterol for membrane structure or steroid hormone synthesis. -LDL reacts with receptors on various cells, is taken up by LDL-receptor – mediated endocytosis (see next slide). The receptors are recognized by apo B100 -Inside cells, LDL is digested by lysosomal enzymes and free cholesterol is released from cholesterol esters. -The released free cholesterol is re-esterified by ACAT to CE and stored for use in cell membrane structure or steroid hormone synthesis. -High LDL indicates high plasma cholesterol and tend to deliver cholesterol to artery walls. High blood LDL is associated with high incidence of heart attacks and strokes so it is called: Bad cholesterol.

13. LDL: receptor-mediated endocytosis

14. Synthesis: HDL is synthesized in liver and intestine Functions: 1- HDL is reservoir of Apo CII and Apo E (transferred apoproteoins). 2- HDL transfer excess cholesterol from tissues to liver to be excreted in bile as free cholesterol or converted into bile acids or passed into intestine and excreted with faces. This process is called “reverse cholesterol transport. - HDL is called Good cholesterol as it remove excess cholesterol from arterial walls into liver to be excreted. High blood HDL is associated with low incidence of heart attacks and strokes

15. Synthesized TAG and Choleserol

16. -Chylomicrons are the lowest of lipoproteins in density and the largest in size, contain the highest lipid (85-90% TAG) and smallest protein contents. -VLDL contains 60% TAG. -LDL contains the highest content of CE (50%) - HDL is the most dense, contain the lowest amount of lipid and the highest of protein (50%). CMVLDLLDLHDL Neutral fat (TG) % 85-906083 Protein %2102250 Phospholipid % 8152030 Cholesterol %5155017 Type of apoprotein Apo B48 apo E apo C Apo B100 apo E apo C apo Bapo A-1 apo E apo C

17. From the Table we can divide lipoprotein according to lipid content into: TAG-rich lipoproteins: - Chylomicrons : transport dietary (exogenous) TAG - VLDL: transport TAG of endogenous (hepatic) synthesis Cholesterol-rich lipoproteins: LDL: transport cholesterol from blood to peripheral tissues/liver HDL: transport cholesterol from tissues to liver

18. Type I hyperlipoproteinemia or familial lipoprotein lipase deficiency Due deficiency of lipoprotein lipase or apo C-II CM, VLDL and TAG are increased in plasma Type II hyperlipidemia or Familial hypercholesterolemia deficiency of functional LDL receptors elevation of plasma cholesterol but plasma TG remains normal Abnormalities in lipoprotein metabolism