m tabolisme3 [Mode de compatibilit ]€¦ · Triacylglycerol Glycerol CH 2OC-R 3 CH 2OH. Hormone...
Transcript of m tabolisme3 [Mode de compatibilit ]€¦ · Triacylglycerol Glycerol CH 2OC-R 3 CH 2OH. Hormone...
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Lipid Metabolism
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Lipid Metabolism
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Fatty Acids
CH3(CH2)nCH2CO2H
OO
O
CH3(CH2)nCH2C-O-R
CH3(CH2)nCH2C-OH H-O-R
O
O
CH3(CH2)nCH2C-OH H-S-R
CH3(CH2)nCH2C-S-R
Ester Thioester
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Release of Fatty Acids from Triacylglycerols
O
O LipasesCHOH
CH2OHCH2OC-R1
CHOC-R2
O
O O O
+
HOC-R3 HOC-R2 HOC-R1
Triacylglycerol Glycerol
CH2OH
CHOHCHOC-R2
CH2OC-R3
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Hormone(Adrenalin, Glucagon, ACTH)
Receptor
ATP c-AMP
AdenylylCyclase
Activates
Lipolysis
Adipose Cell
Activates lipase
Triacylglycerols Glycerol +Fatty acids Blood
Insulinblocks thisstep
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ATP c -AMP AMP
Inactive Kinase Activated Kinase
Inactive Lipase Activated Lipase
P
Adenylyl cyclase Phosphodiesterase
Enhanced by insulinEnhanced by glucagon
Inactive Lipase Activated Lipase
Triacyl-glycerol
Glycerol +Fatty Acids
Phosphatase(Hormone-sensitiveLipase)
Insulin favors formationof the inactive lipase
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Acylglycerol Lipases
TriacylglycerolLipase
DiacylglycerolLipase
OH
Triacylglycerol (TAG)
Diacylglycerol (DAG)
Lipase
OH
OH
MonoacylglycerolLipase
OH
OH
OH
Monoacylglycerol(MAG)
Glycerol
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Beta Oxidation
• Cleavage of fatty acids to acetate in tissues
• Occurs in mitochondria
9 CH3COSCoACO2H
[O] [O] [O] [O] [O][O] [O] [O]
N atomes de carbone N/2 molécules acétylCoA
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Steps in Beta Oxidation
• Fatty Acid Activation by Esterification with CoASH
• Membrane Transport of Fatty Acyl CoA EstersEsters
• Carbon Backbone Reaction Sequence• Dehydrogenation• Hydration• Dehydrogenation• Carbon-Carbon Cleavage (Thiolase Reaction)
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Fatty Acid Activation by Esterification with CoASH
CoASH + RCO 2H + ATP RCOSCoA + AMP + PP i
AcylCoA
Synthetase Pyrophos-phatase
Synthetase
2 Pi
phatase
Occurs in outer mitochondrialmembrane for long chain fatty acids
ATP AMP + PP i -32.3CoASH + RCO 2H RCOSCoA +31.5PPi 2 Pi -33.6
∆∆∆∆G0’(KJ/mole)
-34.4
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Lipid Metabolism
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Membrane Transport of Fatty Acyl CoA Esters
(CH3)3NO
O -OH
Carnitineacyltransferase II(matrix side of inner mitochondrial
Carnitineacyltransferase I(outer part of mitochondrial
Carnitine
+RCOSCoA +
Transported across inner mitochondrial
membrane by translocase
(CH3)3NO
O -O2CR
inner mitochondrialmembrane)
(outer part of mitochondrial inner membrane)
O-Acylcarnitine
+
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Beta Oxidation Reaction SequenceH H
H H
H
H
Enoyl CoA Hydratase
R-CH2-C-C-COSCoA R-CH2-C=C-COSCoA
Acyl CoADehydrogenase
FAD FADH2trans-∆2-enoyl CoA
H2O
L-β-Hydroxyacyl β-Ketoacyl CoA
Occurs in Mitochondria
Repeat Sequence
H H
HO HO
H
O
H
O
R-CH2-C-C-COSCoAR-CH2-C-C-COSCoA
R-CH2-C-SCoA CH3-C-SCoA
L-β-Hydroxyacyl CoA
L-β-Hydroxyacyl CoADehydrogenase
NAD+NADH + H+
CoASH
+
Thiolase
β-Ketoacyl CoA
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Complete Beta Oxidation of Palmitoyl CoA
CH3CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA
7 Cycles7 Cycles
8 CH3COSCoA + 7 FADH 2 + 7 NADH + 7 H+
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Energetics of Complete Oxidation of Fatty Acids
Palmitic Acid Palmitoyl CoA -1
CH COSCoA CO + H O 131
High Energy PhosphateBonds Generated
TCA CycleCH3COSCoA CO 2 + H2O 131
Net 130
TCA Cycle
130 High Energy Phosphate Bonds ∆∆∆∆G0’ = 3965 KJ/Mole
For Palmitic Acid CO 2:∆∆∆∆G0’ = - 9790 KJ/Mole
Efficiencyof ββββ-Oxidation = 25%
ATP = -30.5 KJ/mol
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Beta Oxidation
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Beta Oxidation
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Beta Oxidation of Odd Carbon Fatty Acids (veg)
CH3CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA
5 Cycles
5 CH3COSCoA + CH 3CH2COSCoA
Propionyl CoA
CO2H
COSCoA
H-C-CH3
CO2H
COSCoA
CH3-C-HHO2CCH2CH2COSCoA
D-MethylmalonylCoA
L-MethylmalonylCoA
Succinyl CoA
TCA Cycle
Propionyl CoA CarboxylaseATP/CO2
EpimeraseMutase
Vit. B 12
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Beta Oxidation of Unsaturated Fatty Acids
H H
CH3(CH2)7-C=C-CH2(CH2)6COSCoA
Oleoyl CoABeta Oxidation
H H
CH3(CH2)7-C=C-CH2COSCoA
H
H
CH3(CH2)7-CH2-C=C-COSCoA
Beta Oxidation(3 Cycles)
cis-∆∆∆∆3
Isomerase
trans-∆∆∆∆2
Continuation of Beta Oxidation
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Beta Oxidation of Branched Chain Fatty Acids
CH3 CH3
CH3(CHCH2CH2CH2)3CHCH2CO 2H
Phytanic Acid (from breakdown of chlorophyll)(from breakdown of chlorophyll)
CH3 CH3
OH
CH3(CHCH2CH2CH2)3CHCHCO 2HCH3 CH3
CH3(CHCH2CH2CH2)3CHCO 2H
αααα-Hydroxylase
αααα-Oxidation
(in peroxisomes)
CO2
Pristanic Acid
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Beta Oxidation of Branched Chain Fatty Acids (Cont’d)
CH3 CH3
CH3(CHCH2CH2CH2)3CHCO 2H
Pristanic Acid
CH3 CH3
CH3(CHCH2CH2CH2)3CHCOSCoA
Pristanoyl CoA
Beta Oxidation(6 cycles)
CH3CHCOSCoA + 3 CH 3CH2COSCoA + 3 CH 3COSCoA
CH3
iso-Butyryl CoA Propionyl CoA Acetyl CoA
HO2CCH2CH2COSCoASuccinyl CoA
TCA Cycle