01 metabolisme lipida
TRANSCRIPT
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LIPID METABOLISM
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Lipid Metabolism
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Lipid Metabolism
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Lipid Metabolism
• Digestion - Hydrolysis Reaction
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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 and
release of bile; release of pancreatic enzymes; dec.
gastric motility
2. Secretin - (+) bicarbonate secretion
Digestive Lipid Metabolism
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1. Triacyglycerol hydrolysis
- TAG are acted upon by pancreatic lipase and
removes FA at carbon 1 and 3
- products = 2-monoacylglycerol + FA
2. Cholesteryl ester degradation
- Cholesterol esterase
- Products: Cholesterol + FA
3. Phospholipids degradation
- phospholipase A2
- products: lysophospholipid + FA
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Absorption of Lipids by intestinal mucosal cells
- FFA, free cholesterol, 2-monoacylglycerol and
lysophospholipid together with bile salts from mixed
micelles which is absorbed at the brush border membrane
of SI
- short and medium chain FA are directly absorbed
> Resynthesis of TAG, CE and PL
2-monoacylglycerol + fatty acyl-CoA = TAG
Cholesterol + FA = CE
Lysophospholipid + FA = Phospholipid
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The two
processes
are in many ways
mirror images of
each other.
Steps in Fatty Acid Degradation and Synthesis
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Biosintesis asam lemak
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◘ Fatty acids are synthesized by an
extramitochondrial system (cytosolic)
◘ is present in many tissues :
Liver
Kidney
Brain
Lung
Mammary gland
Adipose tissue
Biosynthesis of Fatty Acids
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Fatty Acid Synthase Multienzyme Complex
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Schematic Representation of Animal Fatty Acid Synthase. Each of the identical chains in the dimer contains three domains. Domain 1 (blue) contains
acetyl 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 flexible
phosphopantetheinyl group (green) carries the fatty acyl chain from one catalytic site on a
chain to another, as well as between chains in the dimer.
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Transfer of Acetyl CoA to the Cytosol. Acetyl CoA is transferred from mitochondria to the cytosol, and the reducing
potential NADH is concomitantly converted into that of NADPH by this series
of reactions.
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Production of Malonyl-CoA Is the Initial &
Controlling Step in Fatty Acid Synthesis
(acetyl-CoA carboxylase)
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Control of Acetyl CoA Carboxylase
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Regulation of acetyl-CoA carboxylase by
phosphorylation/dephosphorylation
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Biosynthesis of
Long-Chain Fatty Acids
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Reactions of Fatty Acid Synthase. Translocations of the elongating fatty acyl chain between the cysteine sulfhydryl
group of the condensing enzyme (CE, blue) and the phosphopantetheine
sulfhydryl group of the acyl carrier protein (ACP, yellow) lead to the growth of
the fatty acid chain.
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PROSES DESATURASI
1. C ≥ 16
2. MULAI DARI C9
3. SELANJUTNYA SELISIH 3 C KEARAH -COOH
C-C-C-C-C-C-C=C-C-C=C-C-C=C-C-COOH
Δ 9 8 7 6 5 4 3 2 1
ASAM LEMAK ESENSIAL
- LINOLEAT 18 Δ 9, 12
- LINOLENAT 18 Δ 9, 12, 15
- ARACHIDONAT 18 Δ 5, 8, 11, 14
Ω
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The Main Source
of NADPH
▪ PPP
▪ Malic enzyme
▪ Isocitrate
dehydrogenase
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Acetyl CoA carboxylase is the key control site in fatty acid synthesis.
Regulation of Fatty Acid Synthesis
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Mobilization of Triacylglycerols
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Degradasi Asam lemak
(penggunaan asam lemak untuk
sumber energi)
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Utilization of Fatty Acids as Fuel
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GLYCEROL METABOLISM
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Lipid Metabolism
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Lipid Metabolism
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carnitine acyltransferase (also called
carnitine palmitoyl transferase I)
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Acyl Carnitine Translocase
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Role of carnitine in the
transport of long-chain
fatty acids through the
inner mitochondrial
membrane.
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Fatty Acid Oxidation
• Initial Step: Requires an ATP to synthesize
acetyl CoA with the fatty acid.
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Beta Oxidation
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Beta Oxidation
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Beta Oxidation
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Beta Oxidation
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Beta Oxidation
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Beta Oxidation
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Beta Oxidation
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Palmitic Acid Review
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2 ATP
3 ATP
n X 12 ATP
(TCA cycle)
(n – 1) X 5 ATP
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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
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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
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Principal reactions in fatty acid oxidation
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Odd-Chain Fatty Acids Yield Propionyl Coenzyme A
Propionyl CoA enters the citric acid cycle
after it has been converted into succinyl CoA.
succinyl CoA
(CYTRIC ACID CYCLE)
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Control of Fatty Acid Degradation
Malonyl CoA inhibits fatty acid degradation by
inhibiting the formation of acyl carnitine.
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Synthesis and Degradation of Triacylglycerols by Adipose Tissue.
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Acetyl CoA
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Lipogenesis
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Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals
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Compartmentation of the Major Pathways of Metabolism.
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Formation of Ketone Bodies.
Acetoacetate spontaneously decarboxylates to form acetone
1) 3-ketothiolase
2) hydroxymethylglutaryl CoA synthase,
3) hydroxymethylglutaryl CoA cleavage enzyme
4) d-3-hydroxybutyrate dehydrogenase
(HMG CoA)
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Formation, utilization, and excretion of ketone bodies.
(The main pathway is indicated by the solid arrows.)
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Utilization of Acetoacetate as a Fuel
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Transport of ketone bodies from the liver and pathways of utilization and
oxidation in extrahepatic tissues.
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Ketone Bodies
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Ketone Bodies
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Blood Glucose and Glucosuria
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Ketone Bodies
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Asam arakhidonat sebagai precursor
hormon prostaglandin
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Arachidonate Is the Major Precursor of Eicosanoid Hormones
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Structures of Several Eicosanoids
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trans- Fatty Acid
Pengaruhnya terhadap metabolisme
asam lemak
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◘ 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.
Trans Fatty Acids Are Implicated in Various Disorders
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KHOLESTEROL
biosintesis dan metabolismenya
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CHOLESTEROL IS DERIVED ABOUT EQUALLY FROM THE DIET
& FROM BIOSYNTHESIS
Acetyl-CoA Is the Source of All Carbon Atoms in Cholesterol
Step 1—Biosynthesis of Mevalonate
Step 2—Formation of Isoprenoid Units
Step 3—Six Isoprenoid Units Form Squalene
Step 4—Formation of Lanosterol
Step 5—Formation of Cholesterol
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Biosynthesis of
mevalonate.
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6 X SQUALENE
LANOSTEROL
CHOLESTEROL
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Transport of cholesterol between the tissues in humans.
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Glycine
Taurine
CHOLESTEROL IS
EXCRETED FROM THE
BODY IN THE BILE AS
CHOLESTEROL OR
BILE ACIDS (SALTS)
Intestinal bacteria produce the
secondary bile acids.
Enterohepatic circulation 98-99%
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Diet Can Play an Important Role in Reducing Serum Cholesterol
corn oil and sunflower seed oil : polyunsaturated and
monounsaturated fatty acids
olive 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
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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 VLDL
Cholesterol and phospholipid are the predominant lipids in LDL and HDL
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Generalized Structure of A Plasma Lipoprotein
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Composition of the lipoproteins in plasma of humans
1Secreted with chylomicrons but transfers to HDL.
2Associated with HDL2 and HDL3 subfractions.
3Part of a minor fraction known as very high density lipoproteins (VHDL).
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Secretion of (A) chylomicrons
by an intestinal cell
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Secretion of (B) very low
density lipoproteins by a
hepatic cell.
SD, space of Disse
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Metabolic fate of chylomicrons
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Metabolic fate of very low density lipoproteins (VLDL) and production of
low-density lipoproteins (LDL)
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Metabolism of high-density lipoprotein (HDL) in reverse
cholesterol transport
LCAT, lecithin:cholesterol acyltransferase; C, cholesterol; CE, cholesteryl ester; PL,
phospholipid; A-I, apolipoprotein A-I; SR-B1, scavenger receptor B1; ABC-1, ATP binding
cassette transporter 1.
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Imbalance in
the Rate of
Triacylglycerol
Formation &
Export Causes
Fatty Liver
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Primary disorders of plasma lipoproteins (dyslipoproteinemias)
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Hypolipidemic Drugs Will Reduce Serum Cholesterol& Triacylglycerol
Cholestyramine 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 ↓
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Metabolism of adipose tissue. Hormone-sensitive lipase is
activated by ACTH, TSH,
glucagon, epinephrine,
norepinephrine, and vasopressin
and inhibited by insulin,
prostaglandin E1, and
nicotinic acid.
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Control of adipose tissue lipolysis.