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Lipoprotein metabolism

Biochemistry from Dr. Dhiraj J Trivedi
SDM College of Medical Sciences and Hospital, Dharwad, India

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Lipoprotein metabolism

  1. 1. Always behave like a DUCK Keep calm and unruffled on the surface But Paddle with great vigor underneath Dr. Dhiraj J. Trivedi
  2. 2. Lipoprotein and its Metabolism
  3. 3. What is lipoproteins? • Lipoproteins are spherical, macromolecular complexes of lipids and specific protein called Apo-protein.
  4. 4. What are the functions of lipoproteins? • 1. They keep water insoluble lipids in solution of aqueous plasma. • 2. Provide mechanism for transporting their lipid components to and from the tissue.
  5. 5. What is the general composition of plasma lipoproteins? They contain neutral lipid core made of TG , Cholesteryl esters and shell of amphipathic phospholipids, Unesterified cholesterol and apoprotein.
  6. 6. HOW ARE THE LIPOPROTEINS CLASSIFIED? Classified on the basis of 1.COMPOSITION 2.DENSITY and 3.ELECTRO PHORETIC MOBILITY
  7. 7. Name the classes of lipoproteins? • 1. Chylomicron • 2. Very low density lipoproteins (VLDL). • 3. Low density lipoproteins (LDL). • 4. High density lipoproteins (HDL). • 5. Free fatty acids – Albumin complex
  8. 8. Arrangement of lipoprotein on their Size and Density Lipoprotein class Size Density Chylomicrone 1000 to 10,000A Less than 0.96 VLDL 300 to 700A Upto 1.006 LDL 150 to 250A Upto 1.063 HDL 75 to 100A Above 1.063
  9. 9. Lipoprotein composition TG C & CE PL Apo protein Chylo- microne 90 % 5 % 3 % 2 % VLDL 60 % 20 % 15 % 5 % LDL 08 % 50 % 22 % 20 % HDL 05 % 25 % 30 % 40 %
  10. 10. Electrophoretic mobilityDensity
  11. 11. Lipoprotein molecule
  12. 12. Write the functions of apolipoproteins. • 1. Provide recognition sites for cell surface receptors. • 2. Serves as coenzymes • 3. Some are required as a structural part and can not be replaced or removed.
  13. 13. Write the functions of CHYLOMICRONES. • Transport mainly Exogenous Tri acyl glycerol from intestine to Liver, adipose tissue and muscle. • TAG either absorbed from food or Synthesized in enterocytes ) Adipose Muscle
  14. 14. Write the functions of Very Low Density Lipoproteins ( VLDL ) • Transports mainly endogenous Tri acyl glycerol from Liver to extra hepatic tissues • Endogenous Tri acyl glycerol Synthesized in hepatocyte
  15. 15. Write the functions of Low Density Lipoproteins (LDL) • Transports mainly Cholesterol and cholesteryl esters from Liver to extra hepatic tissues cholesterol
  16. 16. Write the functions of High Density Lipoproteins (HDL) • Transports mainly Cholesterol and Cholesteryl esters from extra hepatic tissues to Liver • Serves to hold apo- c & apo-e for use cholesterol
  17. 17. Write the functions of Free fatty acid Albumin complex • Transports mainly free fatty acids released from adipose tissue to Liver for oxidation FFA Adipose Adipose Adipose FFA FFA FFA
  18. 18. Enzymes in lipoprotein metabolism • Lecithin cholesterol acyl transferase • L CAT : • Catalyses transfer of Sn2 FA of phospholipids to cholesterol. • Converts polar cholesterol to non polar cholesteryl esters • Shift of cholesterol form periphery to core
  19. 19. • Lipoprotein lipase • Heparin sensitive lipase Catalyses hydrolysis of chylomicron and VLDL Located on capillary surface Responsible for generating FA and glycerol in tissue Enzymes in lipoprotein metabolism
  20. 20. • Hepatic lipase Catalyses hydrolysis of TAG and Phospholipids of HDL and IDL Located in sinusoid s of liver Responsible for metabolic degradation of HDL and IDL Enzymes in lipoprotein metabolism
  21. 21. • Acid lipase • Intracellular lipase Catalyses hydrolysis of TAG and cholesteryl esters in lysosomes Located in lysosome , Optimum pH acidic Responsible for degradation of lipoprotein taken up by receptor mediated endocytosis Enzymes in lipoprotein metabolism
  22. 22. Lipoprotein Receptors E B10 0 E Receptor for chylomicron remnants Receptor for LDL and IDL X unknownReceptor for HDL Receptor for LDL does not recognize VLDL due to presence of C ii Apo C ac t as coenzyme for lipo protein lipase
  23. 23. METABOLISM OF CHYLOMICRONS Lipoprotein metabolism 1
  24. 24. Type I Hyper LP Lplipase def Apo Cii def
  25. 25. METABOLISM OF VLDL AND LDL Lipoprotein metabolism 2
  26. 26. Type III Hyper LP Fatty liver Type II Hyper LPLDL not removed
  27. 27. CELLUAR UPTAKE AND DEGRADATION OF LDL Lipoprotein metabolism 3
  28. 28. Receptor mediated Endocytosis
  29. 29. METABOLISM OF HDL Lipoprotein metabolism 4
  30. 30. VLD L VLD L LCAT
  31. 31. Apo – A1 Apo – B Bad cholesterol LDL Good cholesterol HDL
  32. 32. Lipoproteins and Disease • Hyperlipoproteinemias and hypolipoproteinemias are due to malfunctions in the synthesis and catabolism of lipoproteins.
  33. 33. HYPERLIPOPROTEINEMIA TYPE -- I Deficiency of enzyme lipoprotein lipase VLDL and Chylomicrons are not utilized High TAG level in the blood
  34. 34. HYPERLIPOPROTEINEMIA TYPE -- II Lack of removal of LDL form the blood Not recognising Apo B100 in LDL receptor High Cholesterol level in the blood High risk of CHD and Atherosclerosis
  35. 35. HYPERLIPOPROTEINEMIA TYPE -- III Deficiency of enzyme mobilising VLDL and LDL from circulation Apo E deficient, impairs uptake IDL level increase in the blood
  36. 36. HYPERLIPOPROTEINEMIA TYPE -- IV Due to imbalance between synthesis and clearance of VLDL in circulation
  37. 37. HYPERLIPOPROTEINEMIA TYPE -- V Lipoprotein lipase deficient or utilisation of VLDL and Chylomicrons
  38. 38. HYPO LIPOPROTEINEMIA A BETA LIPOPROTEINEMIA 1. Serum LDL and VLDL level decreased due to absence of Apo B 2. Lack of formation of Chylomicron after high fatty meal 3. Result malabsorption, steatorrhea and cholesterol deposition under skin as nodules
  39. 39. HYPO LIPOPROTEINEMIA – II Tangier disease 1. Deficiency of Serum HDL due to absence of Apo A1 2. Result cholesterol ester deposition in skin , cornea and blood vessels. 3. Increased risk of premature CHD
  40. 40. Diseases Genetic defects Risk LPL defect Reduced level of LPL Pancreatitis Apo C-11 defect Inability to synthesize Apo C-11 Pancreatitis A beta lipoproteinemia Inability to synthesize Apo B Neurological defect An alpha lipoproteinemia Inability to synthesize Apo A Cholesteryl esters storage in abnormal sites Diseases associated with lipoprotein metabolism
  41. 41. Apo B48 Apo A Intestinal mucosa Liver Choesterol Fatty acid Apo A Apo C Apo E E Receptor for chylomicron remnants B48 chylomicron remnants B48E AE C II HDL Ch PL Ch TAG Ch TAG Glycerol Free FA Lipoprotein lipase C IIE Nacent chylomicron A E C II CM Ch PL B48 A 1 2 3 4
  42. 42. Thank you

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Biochemistry from Dr. Dhiraj J Trivedi SDM College of Medical Sciences and Hospital, Dharwad, India

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