CHEMISTRY OF LIPOPROTEINS

CHEMISTRY OF LIPOPROTEINS

1. Lipoproteins Gandham.Rajeev Email:[email protected]

2. Introduction Lipoproteins are molecular complexes that consist of lipids & proteins ( conjugated proteins). Protein part is called apolipoprotein . Usually abbreviated as Lp . They function as transport vehicles for lipids in blood plasma. Lipoproteins deliver the lipid components (cholesterol, TAG etc .) to tissues for utilization.

3. Classification of lipoproteins Depending on the density by ultracentrifugation or electophoretic mobility, the lipoproteins are classified as 5 major types. Chylomicrons-contains apoprotein B48. Very low density lipoproteins (VLDL) or prebeta lipoproteins . Main apoprotein is B-100 .

4. 3. Intermediate density lipoproteins (IDL) or broad-beta lipoproteins. 4. Low density lipoproteins (LDL) or betalipoproteins . Major apoprotein in LDL is B-100 . 5. High density lipoproteins (HDL) or alphalipoproteins . Major apoprotein in HDL is apo -A . Free fatty acids (FFA) or nonesterified fatty acids (NEFA) are complexed with albumin.

5. Chylomicrons Synthesized in the intestine & transport exogenous (dietary) TAGs to various tissues. Contains apoprotein B-48 . They consist of highest (99%) quantity of lipid & lowest (1%) concentration of protein. The chylomicrons are the least in density & largest in size.

6. Very low density lipoproteins (VLDL ) Pre β -lipoproteins. Main apoprotein is B-100. They are produced in liver & intestine . Responsible for the transport of endogenously synthesized triacylglycerols .

7. Low density lipoproteins (LDL ) β -lipoprotein. They are formed from VLDL in the blood circulation. They transport cholesterol from liver to other tissues.

8. High density lipoproteins (HDL ) α-lipoproteins. Major apoprotein in HDL is apo -A. They are mostly synthesized in liver. Three different fractions of HDL (1, 2 & 3) identified by ultracentrifugation . HDL particles transport cholesterol from peripheral tissues to liver (reverse cholesterol transport).

9. Free fatty acids or non-esterified fatty acids Free fatty acids or non-esterified fatty acids (NEFA) are complexed with albumin. Loosely bound to the protein-albumin. Each molecule of albumin can hold about 20-30 molecules of free fatty acids.

10. Structure of lipoproteins L ipoprotein consists of inner core (hydrophobic triacylglycerol, cholesterylester & tails of phospholipids) surrounded by a coat shell of phospholipids, apoproteins & cholesterol.

11. The polar head portions (hydrophilic ) of phospholipids & cholesterol are exposed on the surface of lipoproteins. So that lipoprotein is soluble in aqueous solution. The apoproteins also increase the solubility of lipids.

12. Apo-lipoproteins Protein part of lipoprotein is called as apolipoprotein ( apo-Lp ) or apoprotein . Synthesis: All apoproteins are synthesized in liver. Small quantities are produced from almost all organs. Intestinal cells produce small quantities of apo -A. They will solubilize the lipid part.

13. Functions of apolipoproteins Apo A-1: It activates LCAT. It is the ligand for HDL receptor. It is anti- atherogenic . It is specific for HDL. Apo B-100: Only apoprotein component of LDL. It binds to LDL receptors on tissues.

14. It is one of the biggest proteins, having 4536 amino acids, & molecular weight is 550 kDa . Synthesized in liver. Apo B-48: Major apoprotein of chylomicrons . Synthesized only in intestinal cells. Apo-B-100 & apo-B-48 are products of same gene.

15. In intestine, mRNA undergoes editing, to produce only B-48 protein. B-48 is named because it is only 40% of the size of B-100. Apo-C-II: Activates lipoprotein lipase. Apo-E: Arginine rich protein.

16. Present in chylomicrons, LDL & VLDL. Astrocytes also make apo -E. It is involved in transport of lipids in CNS. Apo-E has I,II,III & IV isoforms . Apo-E-IV is implecated in the development of Alzheimer’s disease. Apo-E is also associated with glomerulopathy .

17. Chylomicrons Synthesis: Formed in intestinal mucosal cells, secreted into the lymphatic system. Rich in triglycerides. When chylomicrons are synthesized by intestinal mucosa, contain apo-B-48 & apo -A . Apo-C & apo -E are added from HDL in blood during transport.

18. Structure of Chylomicrons

19. Metabolism of chylomicrons Site of metabolism: Adipose tissue & skeletal muscle. Half-life in blood is about 1 hour Lipoprotein lipase ( LpL ) is located at endothelial layer of capillaries of adipose tissue, muscles & heart. This enzyme is absent in liver.

20. Apo-CII present in chylomicrons activates LpL . LpL hydrolyzes TGL present in chylomicrons into fatty acids & glycerol. Muscles or adipose tissue cells takes up the liberated fatty acids. Injection of heparin, LpL is released from tissues & lipiemia is cleared.

21. This is called as post-heparin lipolytic activity. Lack of C-II leads to decreased activity of LpL & accumulation of chylomicrons & VLDL. Insulin increases LpL activity. Liver takes up chylomicron remnants: As TGL content is progressively decreased, chylomicrons shink in size.

22. These remnants containing apo-B-48 & apo -E are taken up by hepatic cells by receptor mediated endocytosis. Apo-E binds the hepatic receptors.

23. Chylomicrons Metabolism

24. Functions Transport of dietary TGL from intestine to adipose tissue for storage. T o muscle & heart for their energy needs.

25. Very low density lipoproteins Synthesis: Synthesized in the liver from glycerol & fatty acids & incorporated into VLDL, along with hepatic cholesterol, apo-B-100,C-II & E. Apo-B-100 is major lipoprotein in VLDL. Apo-E & C-II are obtained from HDL in plasma.

26. Metabolism of VLDL Half-life of VLDL is 1 to 3 hrs. In peripheral tissues, apo C-II activates LpL which liberates fatty acids that are taken up by adipose tissue & muscle. The remnant is called as IDL. IDL contains less of TAG & more of cholesterol. IDL further loses TAG, & converted to LDL.

27. This conversion of VLDL to IDL & then to LDL is referred to as lipoprotein cascade pathway IDL is taken up by hepatic receptors. Functions of VLDL. VLDL carries triglycerides (endogenous triglycerides ) from liver to peripheral tissues for energy needs .

28. References Textbook of Biochemistry-U Satyanarayana Textbook of Biochemistry-DM Vasudevan

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