Biochem Lipids II


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(c) Geromil J. Lara, RMT, MSMT

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Biochem Lipids II

  1. 1. LIPIDS – part 2Geromil J. Lara, RMT, MSMT
  2. 2. (2) GLYCERIDES• Phosphatidylcholine (Lecithin) – An amphipathic molecule – Similar to that of soap and detergent molecules – Component of cell membranes – Major phospholipid in pulmonary surfactant – Found in egg yolks and soybeans – As emulsifying agent in ice cream 2
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  4. 4. (2) GLYCERIDES• Phosphatidylethanolamine (Cephalin) – Similar in general structure to lecithin – Amine group bonded to the phosphoryl group is the only difference 4
  5. 5. (3) NONGLYCERIDE LIPIDS• Sphingolipids – Are lipids that are not derived from glycerol – Amphipathic and structural components of cellular membranes – Derived from sphingosine (long chain, N- containing alcohol) • Sphingomyelins • Glycosphingolipids 5
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  7. 7. (3) NONGLYCERIDE LIPIDS• Sphingomyelins – Located throughout the body, but are particularly important structural lipid components of nerve cell membranes – Found in abundance in the myelin sheath the surrounds and insulate cells of the CNS – Role is essential to proper cerebral function and nerve transmission 7
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  9. 9. (3) NONGLYCERIDE LIPIDS• Glycosphingolipids (Glycolipids) – Include the cerebrosides, sulfatides, and gangliosides – Are built on a ceramide backbone structure, which is a fatty acid amide derivative of sphingosine 9
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  11. 11. (3) NONGLYCERIDE LIPIDS• Cerebrosides – Are characterized by the presence of a single monosaccharide head group • Glucocerebroside – found in the membranes of macrophages – Consists of ceramide bonded to the hexose glucose • Galactocerebroside – found almost exclusively in the membranes of brain cells – Consists of ceramide joined to the monosaccharide galactose 11
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  13. 13. (3) NONGLYCERIDE LIPIDS• Steroids – Are members of a large, diverse collection of lipids called the isoprenoids (all of these compounds are built from one or more 5- carbon units called isoprene) – Terpene • Is the general term for lipids that are synthesized from isoprene units • Steroids and bile salts, lipid-soluble vitamins 13
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  15. 15. (3) NONGLYCERIDE LIPIDS• Steroids – Contain the steroid nucleus (steroid carbon skeleton) – Cholesterol • known steroid, found in the membranes 15
  16. 16. (3) NONGLYCERIDE LIPIDS• Cholesterol – Amphipathic – Readily soluble in the hydrophobic region of membranes – Involved in the regulation of the fluidity of the membrane as a result of the nonpolar fused ring – Hydroxyl group is polar – Perhydrocyclopentanophenantrene ring 16
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  18. 18. CHOLESTEROL• Can also exist in an esterified form called cholesteryl ester, with the hydroxyl group conjugated by an ester bond to a fatty acid – No polar groups making them very hydrophobic
  19. 19. CHOLESTEROL• Almost exclusively synthesized by animals, but plants do contain other sterols similar in structure to cholesterol• It is not readily catabolized by most cells, therefore, does not serve as a source of energy• Can be converted in the liver to primary bile acids (e.g. cholic acid) and chenodeoxycholic acid – Promote fat absorption in the intestine by acting as detergent
  20. 20. (3) NONGLYCERIDE LIPIDS• Bile Salts – Are amphipathic derivatives of cholesterol – Synthesized in the liver and stored in the gallbladder • Cholate • Chenodeoxycholate – Emulsifying agent – whose polar hydroxyl groups interact with water and whose hydrophobic regions bind to lipids 20
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  22. 22. (3) NONGLYCERIDE LIPIDS• Steroid Hormones (Sex Hormones) – Testosterone – Progesterone – Estrone, Estrogen, and its derivatives – Cortisone and Cortisol – Aldosterone 22
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  24. 24. (3) NONGLYCERIDE LIPIDS• Waxes – Derived from many different sources and have a variety of chemical compositions, depending on the source • Paraffin wax – Long hydrocarbon tails – extremely hydrophobic – completely insoluble in water – Solid at RT • Lanolin – protective coating for hair and skin (used in skin creams and ointments) 24
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  26. 26. (4) COMPLEX LIPIDS• Complex Lipids – Are bonded to other types of molecules – Lipoproteins • Consist of a core of hydrophobic lipids surrounded by amphipathic proteins, phospholipids, and cholesterol 26
  27. 27. LIPOPROTEINS• Typically spherical in shape and range in size 10 to 1200 nm• Composed of both lipids and proteins, called apolipoproteins
  28. 28. LIPOPROTEINS• The larger the LPP particles have larger core regions (contain relatively more TAG and cholesteryl ester)• The larger the LPP also contain more lipid relative to CHON, therefore, lig hter in density
  29. 29. LIPOPROTEINS• Classification (based on ultracentrifugation) – Chylomicrons [chylos] – Very-low-density LPP [VLDL] – Low-density LPP [LDL] – High-density LPP [HDL]
  30. 30. APOLIPOPROTEINS• Primarily located on the surface of lipoprotein particles• Help maintain the structural integrity of LPP• Serve as ligands for cell receptors• As activators and inhibitors of the various enzymes that modify LPP particles
  31. 31. APOLIPOPROTEINS• Contain a structural motif called an amphipathic helix, which accounts for the ability of these proteins to bind to lipids – Are protein segments arranged in coils so that the hydrophobic amino acid residues interact with lipids – Helix containing hydrophilic amino acid faces away from the lipids and toward the aqueous environment
  32. 32. APOLIPOPROTEINS• Apo A-I – Major protein on HDL – Frequently used as an index of th amount of the antiatherogenic HDL present in plasma• Apo B – Is a large protein with MW 500 kD – Principal protein on LDL, VLDL, and Chylomicrons • Apo B-100 • Apo B-48
  33. 33. APOLIPOPROTEINS• Apo B-100 – Is found on LDL and VLDL – Ligand for the LDL receptor – Critical in the uptake of LDL cells• Apo B-48 – Exclusively found in chylomicrons – Can also be found covalently linked to apo (a), a plasminogen-like protein that is found in a proatherogenic LPP particle called lipoprotein (a) [LP(a)]
  34. 34. APOLIPOPROTEINS• Apo E – Found in LDL, VLDL,a nd HDL – Serves as a ligand for the LDL receptor and the chylomicron remnant receptor – Apo E2 – Apo E3 – Apo E4 • Affect LPP metabolism because they differ in their ability to interact with the LDL receptor
  35. 35. CHYLOMICRONS• Contain apo B-48• Account for the turbidity of postprandial plasma• Readily float to the top of stored plasma and form a creamy layer – chylous, turbid, milky, cloudy, lipemic plasma/serum
  36. 36. CHYLOMICRONS• Produced by the intestine, where they are packaged with absorbed dietary lipids• Once enter the circulation, TAG and cholesteryl esters are hydrolyzed by lipase• Are transformed into chylomicron remnant particles, which are taken up by remnant receptors in the liver• Deliver dietary (exogenous) lipids to hepatic and peripheral cells
  37. 37. VERY-LOW-DENSITY LIPOPROTEIN• Contain apo B-100, apo E, and apo C• Produced by the liver• Rich in TAG like chylomicrons• Readily reflect light• Account for most of the turbidity observed in fasting hyperlipidemic plasma specimens but do not form a top, creamy layer
  38. 38. VERY-LOW-DENSITY LIPOPROTEIN• Major carriers of endogenous (hepatic derived) triglycerides• Transfer TAG from the liver to peripheral tissue• Excess dietary intake of CHO, saturated fatty acids, and trans fatty acids enhances the hepatic synthesis of TAG, thus, increases VLDL production
  39. 39. LOW-DENSITY LIPOPROTEIN• Contains apo B-100 and apo E• More cholesterol-rich than other apo B- containing lipoproteins• Primarily form as a consequence of the lipolysis of VLDL• Readily taken up by cells via the LDL receptor – Accounts for the reason that elevated LDL levels promote atherosclerosis
  40. 40. LOW-DENSITY LIPOPROTEIN• Significantly smaller than VLDL and chylomicrons• Can infiltrate into the extracellular space of the vessel wall, where it can be oxidized and taken up by macrophages – Become filled up with intracellular lipid drops and turn into foam cells • an early precursor of atherosclerotic plaques
  41. 41. HIGH-DENSITY LIPOPROTEIN• Smallest and the most dense• Synthesized by both the liver and intestine• Can exist either as disk-shaped or as spherical-shaped particles• Discoidal HDL – Contains 2 molecules of apo A-I – Represent newly secreted HDL – Most active form in removing excess cholesterol from peripheral cells
  42. 42. HIGH-DENSITY LIPOPROTEIN• Discoidal HDL – Acquire additional lipid, cholesteryl esters, and TAG form a core region between the central lipid bilayer, which transforms into spherical HDL (predominant form in plasma)• Spherical HDL – HDL2 • Larger in size and richer in lipid than HDL3 • May be more efficient in delivering lipids to the liver – HDL3
  43. 43. REFERENCE RANGES ANALYTE REFERENCE RANGETotal Cholesterol 140 – 200 mg/dLHDL Cholesterol 40 – 75 mg/dLLDL Cholesterol 50 – 130 mg/dLTriglycerides 60 – 150 mg/dL