5. Digestive Lipid MetabolismEmulsification 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. 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. 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. Steps in Fatty Acid Degradation and Synthesis The two processes are in many ways mirror images of each other.
9. Biosintesis asam lemak
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. Fatty Acid Synthase Multienzyme Complex
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. 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. Production of Malonyl-CoA Is the Initial & Controlling Step in Fatty Acid Synthesis(acetyl-CoA carboxylase)
15. Control of Acetyl CoA Carboxylase
16. Regulation of acetyl-CoA carboxylase by phosphorylation/dephosphorylation
17. Biosynthesis ofLong-Chain Fatty Acids
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.
30. Role of carnitine in thetransport of long-chainfatty acids through theinner mitochondrialmembrane.
31. Fatty Acid Oxidation• Initial Step: Requires an ATP to synthesize acetyl CoA with the fatty acid.
32. Beta Oxidation
33. Beta Oxidation
34. Beta Oxidation
35. Beta Oxidation
36. Beta Oxidation
37. Beta Oxidation
38. Beta Oxidation
39. Palmitic Acid Review
40. 2 ATP 3 ATP(n – 1) X 5 ATPn X 12 ATP(TCA cycle)
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. 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. Principal reactions in fatty acid oxidation
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. Control of Fatty Acid DegradationMalonyl CoA inhibits fatty acid degradation byinhibiting the formation of acyl carnitine.
46. Synthesis and Degradation of Triacylglycerols by Adipose Tissue.
47. Acetyl CoA
49. Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals
50. Compartmentation of the Major Pathways of Metabolism.
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. Formation, utilization, and excretion of ketone bodies.(The main pathway is indicated by the solid arrows.)
53. Utilization of Acetoacetate as a Fuel
54. Transport of ketone bodies from the liver and pathways of utilization andoxidation in extrahepatic tissues.
55. Ketone Bodies
56. Ketone Bodies
57. Blood Glucose and Glucosuria
58. Ketone Bodies
59. Asam arakhidonat sebagai precursor hormon prostaglandin
60. Arachidonate Is the Major Precursor of Eicosanoid Hormones
61. Structures of Several Eicosanoids
62. trans- Fatty AcidPengaruhnya terhadap metabolisme asam lemak
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. KHOLESTEROLbiosintesis dan metabolismenya
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. Biosynthesis ofmevalonate.
67. 6X SQUALENE LANOSTEROL CHOLESTEROL
68. Transport of cholesterol between the tissues in humans.
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. 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. 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. Generalized Structure of A Plasma Lipoprotein
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. Secretion of (A) chylomicronsby an intestinal cell
75. Secretion of (B) very lowdensity lipoproteins by ahepatic cell. SD, space of Disse
76. Metabolic fate of chylomicrons
77. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL)
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.