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
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
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
Steps in Fatty Acid Degradation and Synthesis The two processes are in many ways mirror images of each other.
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.
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.
Production of Malonyl-CoA Is the Initial & Controlling Step in Fatty Acid Synthesis(acetyl-CoA carboxylase)
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.
2 ATP 3 ATP(n – 1) X 5 ATPn X 12 ATP(TCA cycle)
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
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
Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals
Compartmentation of the Major Pathways of Metabolism.
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
Formation, utilization, and excretion of ketone bodies.(The main pathway is indicated by the solid arrows.)
trans- Fatty AcidPengaruhnya terhadap metabolisme asam lemak
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.
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
Transport of cholesterol between the tissues in humans.
CHOLESTEROL ISEXCRETED FROM THEBODY IN THE BILE ASCHOLESTEROL ORBILE ACIDS (SALTS) Glycine Taurine Intestinal bacteria produce the secondary bile acids. Enterohepatic circulation 98-99%
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
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
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).
Secretion of (A) chylomicronsby an intestinal cell
Secretion of (B) very lowdensity lipoproteins by ahepatic cell. SD, space of Disse