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Lipoprotein metabolism

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Lecture slides on Lipoprotein metabolism

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Lipoprotein metabolism

  1. 1. Department of Biochemistry, Nepalgunj Medical College, Nepal Formation and secretion Sunday, July 10, 2016 Rajesh Chaudhary 1
  2. 2. Biomedical importance Lipoprotein mobilization and utilization after oxidation during the energy requirement process or stage. Abnormalities in lipoprotein metabolism leads to either hypo- or hyperlipoproteinemia. Example: Hypertriacylglycerolemia during T2DM. Hypercholesterolemia and premature atherosclerosis. Sunday, July 10, 2016 Rajesh Chaudhary 2
  3. 3. Plasma consists of: triacylglycerol (16%), phospholipids (30%), cholesterol (14%), cholesterol ester (36%), and free fatty acids (4%). Sunday, July 10, 2016 Rajesh Chaudhary 3 4 major lipid classes
  4. 4. 1. Chylomicrons 2. VLDL 3. LDL 4. HDL Sunday, July 10, 2016 Rajesh Chaudhary 4 4 major plasma lipoproteins
  5. 5. Lipoprotein particle Sunday, July 10, 2016 Rajesh Chaudhary 5
  6. 6. Lipoprotein particle Sunday, July 10, 2016 Rajesh Chaudhary 6
  7. 7. Density of lipoproteins Sunday, July 10, 2016 Rajesh Chaudhary 7 𝐋𝐢𝐩𝐢𝐝 𝐏𝐫𝐨𝐭𝐞𝐢𝐧 If, Is high, density is lower and vice- versa.
  8. 8. Plasma lipoproteins Spherical macromolecular complexes of lipids + specific proteins (apolipoproteins / apoproteins) Examples: Chylomicrons, VLDL, LDL, HDL. Lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). Sunday, July 10, 2016 Rajesh Chaudhary 8
  9. 9. The distribution of apolipoproteins characterizes the lipoproteins Of HDL: Apolipoprotein A Of VLDL and LDL: apolipoprotein B (B-100) Of Chylomicrons: apolipoprotein B (B-48) – truncated form of apolipoprotein B. Apo C I, C II, C III and apoE are freely transferrable between lipoproteins. NOTE: B-100 is synthesized in liver while B-48 in intestine. Sunday, July 10, 2016 Rajesh Chaudhary 9
  10. 10. So, what are the functions of apolipoproteins? 1. They can form part of the structure of lipoproteins. 2. They are enzyme cofactors. (C-II for lipoprotein lipase) 3. They acts as ligands to interact with the receptors in tissues. Sunday, July 10, 2016 Rajesh Chaudhary 10
  11. 11. Formation and secretion of Chylomicrons and VLDL Sunday, July 10, 2016 Rajesh Chaudhary 11 ApoB ApoB + lipoprot ein ApoB + lipoprote in +carboh ydrates
  12. 12. Formation and secretion mechanism of both Chylomicrons and VLDL are common. Why? Sunday, July 10, 2016 Rajesh Chaudhary 12
  13. 13. NOTE: The inability of particulate lipid of the size of chylomicrons and VLDL to pass through endothelial cells of capillaries without prior hydrolysis is probably the reason dietary fat enters the circulation through lymphatic and not through the hepatic portal system. Sunday, July 10, 2016 Rajesh Chaudhary 13 -- Harper’s Illustrated Biochemistry
  14. 14. Abetalipoproteinemia and apoB ApoB is not able to function because of a defect in a triacylglycerol transfer protein which prevents loading of the apoB with lipid; therefore, lipoprotein containing this apolipoprotein are not formed, and lipid droplets accumulate in the intestine and liver. Sunday, July 10, 2016 Rajesh Chaudhary 14
  15. 15. Characteristics of abetalipoproteinemia  Vitamin deficiency because of inability of the cells to absorb vitamins – particularly fat-soluble vitamins – Vit. E in particular. Failure to gain weight, growth retardation, diarrhea, abnormal star-shaped RBC, fatty, foul-smelling stools. Impaired nervous system, poor muscle coordination, ataxia, progressive degeneration of retina. Sunday, July 10, 2016 Rajesh Chaudhary 15
  16. 16. Catabolism of chylomicrons and VLDL Chylomicrons and VLDL are very rapidly metabolized. Triacylglycerol of chylomicrons and VLDL are hydrolyzed by lipoprotein lipase. The action of lipoprotein lipase forms remnant lipoproteins. The liver is responsible for the uptake of remnant lipoproteins. Sunday, July 10, 2016 Rajesh Chaudhary 16
  17. 17. Sunday, July 10, 2016 Rajesh Chaudhary 17 Metabolism of
  18. 18. Lipoprotein lipase 1. Located on the wall of blood capillaries, anchored to the endothelium by negatively charged proteoglycan chain of heparin sulfate. 2. Found in: Heart, adipose tissue, renal medulla, lungs, aorta, diaphragm, lactating mammary gland and neonatal liver. 3. Not active in adult liver. Sunday, July 10, 2016 Rajesh Chaudhary 18
  19. 19. Sunday, July 10, 2016 Rajesh Chaudhary 19
  20. 20. Rajesh Chaudhary 20 Metabolic fate of chylomicrons
  21. 21. Sunday, July 10, 2016 Rajesh Chaudhary 21 Metabolism of
  22. 22. Sunday, July 10, 2016 Rajesh Chaudhary 22
  23. 23. Sunday, July 10, 2016 23 Metabolic fate of VLDL and formation of LDL Receptors are defective in familial hypercholesterolemia.
  24. 24. Sunday, July 10, 2016 Rajesh Chaudhary 24 Metabolism of
  25. 25. Sunday, July 10, 2016
  26. 26. Sunday, July 10, 2016 Rajesh Chaudhary 26 Metabolism of HDL
  27. 27. Sunday, July 10, 2016 Rajesh Chaudhary 27

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