Lipid Metabolism
Lipid Metabolism
Lipid Metabolism
1. Classification of lipids
2. Hydrolysis of triglycerids
3. Oxidation of fatty acids
4. Biosynthesis of fatty acids
CLASSIFICATION OF LIPIDS
FUNCTIONS OF LIPIDS
Fatty Acids
CH3(CH2)nCH2CO2H
O O
CH3(CH2)nCH2C-OH H-O-R CH3(CH2)nCH2C-OH H-S-R
O O
CH3(CH2)nCH2C-O-R CH3(CH2)nCH2C-S-R
Ester Thioester
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KATABOLISM OF LIPIDS
ANABOLISM OF LIPIDS (BIOSYNTHESIS)
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Release of Fatty Acids from Triglycerids
O
CH2OC-R1 CH2OH
O Lipases
CHOC-R2 CHOH
O
CH2OC-R3 CH2OH
Triacylglycerol Glycerol
+
O O O
HOC-R1 HOC-R2 HOC-R3
Acylglycerol (Triglyceride) Lipases
Diacylglycerol (DAG)
Triacylglycerol
Lipase
OH
Triacylglycerol (TAG) Diacylglycerol
Lipase
OH OH
Monoacylglycerol
Lipase
OH
Monoacylglycerol
OH OH (MAG)
Glycerol
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GLYCEROL METABOLISM
Fatty Acid Oxidation
Fatty acid degradation occurs in the mitochondria and yields acetyl CoA
and reduced cofactors via β-oxidation.
Subsequent oxidation of these products by the TCA (Krebs) cycle and the
electron transport pathway yields ATP.
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Steps in Beta Oxidation
• Fatty Acid Activation by Esterification with
CoASH
• Membrane Transport of Fatty Acyl CoA Esters
• Carbon Backbone Reaction Sequence
• Dehydrogenation
• Hydration
• Dehydrogenation
• Carbon-Carbon Cleavage (Thiolase Reaction)
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Fatty Acid Activation by Esterification with CoASH
AcylCoA
+ O
RCOSCoA +(CH3)3N
O-
OH
Carnitine Carnitine
Carnitine
acyltransferase II acyltransferase I
(matrix side of (outer part of mitochondrial
inner mitochondrial inner membrane)
membrane)
+ O
(CH3)3N
O-
O2CR
O-Acylcarnitine
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Translocase
Source: http://cellbio.utmb.edu/cellbio/mitochondria_1.htm 23
Beta Oxidation Reaction Sequence
Acyl CoA
HH Dehydrogenase H
R-CH2-C-C-COSCoA R-CH2-C=C-COSCoA
HH FAD FADH H - 2-enoyl CoA
trans
2
H2O
Enoyl CoA Hydratase
L--Hydroxyacyl
-Ketoacyl CoA
CoA HH
H Dehydrogenase
R-CH -C-C-COSCoA R-CH2-C-C-COSCoA
2
OH HO H L--Hydroxyacyl CoA
NADH NAD+
+ H+
CoASH
Thiolase
Repeat Sequence
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Complete Beta Oxidation of Palmitoyl CoA
CH3CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA
7 Cycles
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Energetics of Complete Oxidation of Fatty Acids
Net 106
106 High Energy Phosphate Bonds G0’ = 3,233 KJ/Mole
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Beta Oxidation of Odd Carbon Fatty Acids
CH3CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA
5 Cycles
5 CH3COSCoA + CH3CH2COSCoA
Propionyl CoA
Propionyl CoA Carboxylase
TCA Cycle ATP/CO2
CO2H CO2H
Mutase Epimerase
H H
CH3(CH2)7-C=C-CH2(CH2)6COSCoA
Oleoyl CoA
Beta Oxidation
(3 Cycles)
H
H H Isomerase
CH3(CH2)7-C=C-CH2COSCoA CH3(CH2)7-CH2-C=C-COSCoA
cis-3 trans- 2 H
Thiolase
2 CH3COSCoA CH3COCH2COSCoA CH3COSCoA
Acetoacetyl CoA
HMG CoA
Synthase
Several
Cholesterol steps OH
(in cytosol)
HO2C-CH2-C-CH2COSCoA
CH3
(in liver: mitochon-
drial matrix) Ketogenesis -Hydroxy--methylglutaryl CoA
(HMG CoA)
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Ketogenesis: Formation of Ketone Bodies (Cont’d.)
OH
HMG CoA
HO2C-CH2-C-CH2COSCoA lyase
CH3COCH2CO2
CH3 - CH3COSCoA Acetoacetate
HMG CoA NADH + H+
Dehydrogenase - CO2
+
NAD
OH
CH3COCH3
CH3CHCH2CO2
Acetone
-Hydroxybutyrate (volatile)
Thiolase
Succinate
2 Acetyl CoA Acetoacetyl CoA
Combines with
oxaloacetate
TCA Cycle
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OVERVIEW OF METABOLISM
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Overview of Metabolism
In metabolism:
• Catabolic pathways degrade large molecules.
• Anabolic pathway synthesize molecules.
• Branch points determine which compounds are
degraded to acetyl CoA to meet energy needs or
converted to glycogen for storage.
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The End