01 metabolisme lipida

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01 metabolisme lipida

  1. 1. LIPID METABOLISM
  2. 2. Lipid Metabolism
  3. 3. Lipid Metabolism
  4. 4. Lipid Metabolism• Digestion - Hydrolysis Reaction
  5. 5. Digestive Lipid MetabolismEmulsification of Dietary lipids in the small intestines - emulsification inc. the surface area lipase activity - detergent property of bile salt and peristalsis> Pancreatic activity Hormonal Control of Lipid Digestion 1. CCK/pancreozymin – (+)GB contraction andrelease of bile; release of pancreatic enzymes; dec.gastric motility 2. Secretin - (+) bicarbonate secretion
  6. 6. 1. Triacyglycerol hydrolysis - TAG are acted upon by pancreatic lipase and removes FA at carbon 1 and 3 - products = 2-monoacylglycerol + FA2. Cholesteryl ester degradation - Cholesterol esterase - Products: Cholesterol + FA3. Phospholipids degradation - phospholipase A2 - products: lysophospholipid + FA
  7. 7. Absorption of Lipids by intestinal mucosal cells- FFA, free cholesterol, 2-monoacylglycerol andlysophospholipid together with bile salts from mixedmicelles which is absorbed at the brush border membraneof SI- short and medium chain FA are directly absorbed> Resynthesis of TAG, CE and PL2-monoacylglycerol + fatty acyl-CoA = TAGCholesterol + FA = CELysophospholipid + FA = Phospholipid
  8. 8. Steps in Fatty Acid Degradation and Synthesis The two processes are in many ways mirror images of each other.
  9. 9. Biosintesis asam lemak
  10. 10. Biosynthesis of Fatty Acids◘ Fatty acids are synthesized by an extramitochondrial system (cytosolic)◘ is present in many tissues : Liver Kidney Brain Lung Mammary gland Adipose tissue
  11. 11. Fatty Acid Synthase Multienzyme Complex
  12. 12. Schematic Representation of Animal Fatty Acid Synthase.Each of the identical chains in the dimer contains three domains. Domain 1 (blue) containsacetyl transferase (AT), malonyl transferase (MT), and condensing enzyme (CE). Domain 2(yellow) contains acyl carrier protein (ACP), b-ketoacyl reductase (KR), dehydratase (DH),and enoyl reductase (ER). Domain 3 (red) contains thioesterase (TE). The flexiblephosphopantetheinyl group (green) carries the fatty acyl chain from one catalytic site on achain to another, as well as between chains in the dimer.
  13. 13. Transfer of Acetyl CoA to the Cytosol.Acetyl CoA is transferred from mitochondria to the cytosol, and the reducingpotential NADH is concomitantly converted into that of NADPH by this seriesof reactions.
  14. 14. Production of Malonyl-CoA Is the Initial & Controlling Step in Fatty Acid Synthesis(acetyl-CoA carboxylase)
  15. 15. Control of Acetyl CoA Carboxylase
  16. 16. Regulation of acetyl-CoA carboxylase by phosphorylation/dephosphorylation
  17. 17. Biosynthesis ofLong-Chain Fatty Acids
  18. 18. Reactions of Fatty Acid Synthase.Translocations of the elongating fatty acyl chain between the cysteine sulfhydrylgroup of the condensing enzyme (CE, blue) and the phosphopantetheinesulfhydryl group of the acyl carrier protein (ACP, yellow) lead to the growth ofthe fatty acid chain.
  19. 19. PROSES DESATURASI 1. C ≥ 16 2. MULAI DARI C9 3. SELANJUTNYA SELISIH 3 C KEARAH -COOH Ω Δ9 8 7 6 5 4 3 2 1 C-C-C-C-C-C-C=C-C-C=C-C-C=C-C-COOHASAM LEMAK ESENSIAL - LINOLEAT 18 Δ 9, 12 - LINOLENAT 18 Δ 9, 12, 15 - ARACHIDONAT 18 Δ 5, 8, 11, 14
  20. 20. The Main Source of NADPH▪ PPP▪ Malic enzyme▪ Isocitrate dehydrogenase
  21. 21. Regulation of Fatty Acid SynthesisAcetyl CoA carboxylase is the key control site in fatty acid synthesis.
  22. 22. Mobilization of Triacylglycerols
  23. 23. Degradasi Asam lemak(penggunaan asam lemak untuk sumber energi)
  24. 24. Utilization of Fatty Acids as Fuel
  25. 25. GLYCEROL METABOLISM
  26. 26. Lipid Metabolism
  27. 27. Lipid Metabolism
  28. 28. carnitine acyltransferase (also calledcarnitine palmitoyl transferase I)
  29. 29. Acyl Carnitine Translocase
  30. 30. Role of carnitine in thetransport of long-chainfatty acids through theinner mitochondrialmembrane.
  31. 31. Fatty Acid Oxidation• Initial Step: Requires an ATP to synthesize acetyl CoA with the fatty acid.
  32. 32. Beta Oxidation
  33. 33. Beta Oxidation
  34. 34. Beta Oxidation
  35. 35. Beta Oxidation
  36. 36. Beta Oxidation
  37. 37. Beta Oxidation
  38. 38. Beta Oxidation
  39. 39. Palmitic Acid Review
  40. 40. 2 ATP 3 ATP(n – 1) X 5 ATPn X 12 ATP(TCA cycle)
  41. 41. Palmitic Acid -ATP Synthesis• Palmitic Acid is C-16• Initiating Step - requires 1 ATP (text says 2)• Step 1 - FAD into e.t.c. = 2 ATP• Step 3 - NAD+ into e.t.c. = 3 ATP• Total ATP per turn of spiral = 5 ATP• Example with Palmitic Acid = 16 carbons = 8 acetyl groups• Number of turns of fatty acid spiral = 8-1 = 7 turns• ATP from fatty acid spiral = 7 turns and 5 per turn = 35 ATP.• NET ATP from Fatty Acid Spiral = 35 - 1 = 34 ATP
  42. 42. Palmitic Acid (C-16) -ATP Synthesis• NET ATP - Fatty Acid Spiral = 35 - 1 = 34 ATP• Review ATP - Citric Acid Cycle start with Acetyl CoA• Step ATP produced• 7 visible ATP 1• Step 4 (NAD+ to E.T.C.) 3• Step 6 (NAD+ to E.T.C.) 3• Step10 (NAD+ to E.T.C.) 3• Step 8 (FAD to E.T.C.) 2• NET 12 ATP per turn C.A.C.• 8 Acetyl CoA = 8 turns C.A.C.• 8 turns x 12 ATP/C.A.C. = 96 ATP• GRAND TOTAL 130 ATP
  43. 43. Principal reactions in fatty acid oxidation
  44. 44. Odd-Chain Fatty Acids Yield Propionyl Coenzyme A succinyl CoA (CYTRIC ACID CYCLE) Propionyl CoA enters the citric acid cycle after it has been converted into succinyl CoA.
  45. 45. Control of Fatty Acid DegradationMalonyl CoA inhibits fatty acid degradation byinhibiting the formation of acyl carnitine.
  46. 46. Synthesis and Degradation of Triacylglycerols by Adipose Tissue.
  47. 47. Acetyl CoA
  48. 48. Lipogenesis
  49. 49. Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals
  50. 50. Compartmentation of the Major Pathways of Metabolism.
  51. 51. Formation of Ketone Bodies. (HMG CoA)1) 3-ketothiolase2) hydroxymethylglutaryl CoA synthase,3) hydroxymethylglutaryl CoA cleavage enzyme4) d-3-hydroxybutyrate dehydrogenaseAcetoacetate spontaneously decarboxylates to form acetone
  52. 52. Formation, utilization, and excretion of ketone bodies.(The main pathway is indicated by the solid arrows.)
  53. 53. Utilization of Acetoacetate as a Fuel
  54. 54. Transport of ketone bodies from the liver and pathways of utilization andoxidation in extrahepatic tissues.
  55. 55. Ketone Bodies
  56. 56. Ketone Bodies
  57. 57. Blood Glucose and Glucosuria
  58. 58. Ketone Bodies
  59. 59. Asam arakhidonat sebagai precursor hormon prostaglandin
  60. 60. Arachidonate Is the Major Precursor of Eicosanoid Hormones
  61. 61. Structures of Several Eicosanoids
  62. 62. trans- Fatty AcidPengaruhnya terhadap metabolisme asam lemak
  63. 63. Trans Fatty Acids Are Implicated in Various Disorders◘ Trans-unsaturated fatty acids are found in ruminant fat (eg, butter fat has 2–7%), where they arise from the action of microorganisms in the rumen,◘ Main source in the human diet is from partially hydrogenated vegetable oils (eg, margarine).◘ Trans fatty acids compete with essential fatty acids, exacerbate essential fatty acid deficiency.◘ Structurally similar to saturated fatty acids, have comparable effects in the promotion of hypercholesterolemia and atherosclerosis.
  64. 64. KHOLESTEROLbiosintesis dan metabolismenya
  65. 65. CHOLESTEROL IS DERIVED ABOUT EQUALLY FROM THE DIET & FROM BIOSYNTHESISAcetyl-CoA Is the Source of All Carbon Atoms in CholesterolStep 1—Biosynthesis of MevalonateStep 2—Formation of Isoprenoid UnitsStep 3—Six Isoprenoid Units Form SqualeneStep 4—Formation of Lanosterol Step 5—Formation of Cholesterol
  66. 66. Biosynthesis ofmevalonate.
  67. 67. 6X SQUALENE LANOSTEROL CHOLESTEROL
  68. 68. Transport of cholesterol between the tissues in humans.
  69. 69. CHOLESTEROL ISEXCRETED FROM THEBODY IN THE BILE ASCHOLESTEROL ORBILE ACIDS (SALTS) Glycine Taurine Intestinal bacteria produce the secondary bile acids. Enterohepatic circulation 98-99%
  70. 70. Diet Can Play an Important Role in Reducing Serum Cholesterolcorn oil and sunflower seed oil : polyunsaturated and monounsaturated fatty acidsolive oil : high concentration of monounsaturated fatty acids. poly and monounsaturated up-regulation of LDL receptors catabolic rate of LDL (LDL = the main atherogenic lipoprotein). cholesterol
  71. 71. Four Major Groups of Plasma Lipoproteins Have Been Identified 1. Chylomicrons : TG (intestinal absorption) 2. VLDL or pre-β-lipoproteins : TG (from the liver) 3. LDL or β-lipoproteins : the catabolism of VLDL 4. HDL or α-lipoproteins : in VLDL / chylomicron metabolism and cholesterol transport.Triacylglycerol is the predominant lipid in chylomicrons and VLDLCholesterol and phospholipid are the predominant lipids in LDL and HDL
  72. 72. Generalized Structure of A Plasma Lipoprotein
  73. 73. Composition of the lipoproteins in plasma of humans1Secreted with chylomicrons but transfers to HDL.2Associated with HDL2 and HDL3 subfractions.3Part of a minor fraction known as very high density lipoproteins (VHDL).
  74. 74. Secretion of (A) chylomicronsby an intestinal cell
  75. 75. Secretion of (B) very lowdensity lipoproteins by ahepatic cell. SD, space of Disse
  76. 76. Metabolic fate of chylomicrons
  77. 77. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL)
  78. 78. Metabolism of high-density lipoprotein (HDL) in reverse cholesterol transportLCAT, lecithin:cholesterol acyltransferase; C, cholesterol; CE, cholesteryl ester; PL,phospholipid; A-I, apolipoprotein A-I; SR-B1, scavenger receptor B1; ABC-1, ATP bindingcassette transporter 1.
  79. 79. Imbalance inthe Rate ofTriacylglycerolFormation &Export CausesFatty Liver
  80. 80. Primary disorders of plasma lipoproteins (dyslipoproteinemias)
  81. 81. Hypolipidemic Drugs Will Reduce Serum Cholesterol& TriacylglycerolCholestyramine resin : bile acids reabsorption ↓ (small intestine) bile acid synthesis ↑(liver) cholesterol excretion ↑ up-regulates LDL receptors plasma cholesterol.Sitosterol : absorption of cholesterol from the gastrointestinal tract ↓.Statins : inhibit HMG-CoA reductase, thus up-regulating LDL receptors. (atorvastatin, simvastatin, and pravastatin.)Clofibrate and gemfibrozil : 1. VLDL secretion ↓, plasma triacylglycerols ↓. 2. stimulate hydrolysis of VLDL triacylglycerols by lipoprotein lipase.Probucol : LDL catabolism ↑, accumulation of oxidized LDL ↓Nicotinic acid : adipose tissue lipolysis ↓, FFA ↓, VLDL ↓
  82. 82. Metabolism of adipose tissue.Hormone-sensitive lipase isactivated by ACTH, TSH,glucagon, epinephrine,norepinephrine, and vasopressinand inhibited by insulin,prostaglandin E1, andnicotinic acid.
  83. 83. Control of adipose tissue lipolysis.

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