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TRANSCRIPT
Lipid Metabolism
Lipid Metabolism
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
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
Hormone(Adrenalin, Glucagon, ACTH)
Receptor
ATP c-AMP
AdenylylCyclase
Activates
Lipolysis
Adipose Cell
Activates lipase
Triacylglycerols Glycerol +Fatty acids Blood
Insulinblocks thisstep
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
Acylglycerol Lipases
TriacylglycerolLipase
DiacylglycerolLipase
OH
Triacylglycerol (TAG)
Diacylglycerol (DAG)
Lipase
OH
OH
MonoacylglycerolLipase
OH
OH
OH
Monoacylglycerol(MAG)
Glycerol
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
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)
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
Lipid Metabolism
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
+
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
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+
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
Beta Oxidation
Beta Oxidation
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
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
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
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