Fatty Acid Synthesis
[Pages:14]Fatty Acid Synthesis
? Requires ? Carbon Source: Acetyl CoA ? Reducing Power: NADPH ? Energy Input: ATP
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Why Energy ?
Fatty Acid
Acetyl CoA Go : -ve
Acetyl CoA
Fatty Acid Go : +ve
1
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Why Energy ?
Fatty Acid
Acetyl CoA Go : -ve
Acetyl CoA + n(ATP)
Fatty Acid + n(ADP) Go : -ve
FA Degradation and Synthesis
Acyl CoA (n)
Oxidation
Acyl CoA (n+2)
reduction
Hydration
dehydration
Oxidation
reduction
Thyolysis
condensation
Acyl CoA (n-2) + Acetyl CoA Acyl CoA(n) + Malonyl CoA
Acetyl CoA
2
Carboxylation of Acetyl CoA Produces Malonyl CoA
O
CH3-C-CoA
O
O
-OC -CH2-C-CoA
CO2 ATP
ADP + Pi
Acetyl CoA Carboxylase Biotin-Containing Enzyme
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Fatty Acid Synthase Catalyzes the remaining steps
? Multifunctional Enzyme Complex ? Dimer of two Identical Chains ? Each has Seven Catalytic Activities
? One activity is Condensing Enzyme with ?SH ? One Domain is Linked to Phosphopantetheine
? With Reactive -SH
3
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2 phosphate
s
Adenine
Ribose
Pantothenic acid
Fatty Acid Synthase Catalyzes the remaining steps
? Multifunctional Enzyme Complex ? Dimer of two Identical Chains ? Each has Seven Catalytic Activities
? One activity is Condensing Enzyme with ?SH ? One Domain is Linked to Phosphopantetheine
? With Reactive -SH ? Carries Intermediates during Catalysis ? (Acyl, Acetyl and Malonyl Groups) ? Known as Acyl Carrier Protein (ACP)
4
Fatty Acid Synthesis (Overview)
Acetyl-CE (Acyl-CE) + Malonyl ACP
(n)
(3)
CO2
Ketoacyl ACP (n+2)
Acyl ACP
CH3CO~S-CE + OOC-CH2-CO~ACP
Acetyl
Malonyl-ACP
(Acyl)
CO2 HS-CE
O CH3C-CH2-CO~ACP
Ketoacyl- ACP
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Reduction of the Ketoacyl Group
O
CH3C-CH2-CO~ACP
Ketoacyl- ACP
NADPH
OH l CH3CH-CH2H2O CH3CH=CH-
NADPH
CH3CH2-CH2-CO~ACP
Synthesis of Palmitate by Fatty Acid Synthase
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Synthesis of Palmitate by Fatty Acid Synthase (Cont.)
Synthesis of Palmitate (net reaction)
How many cycles of synthesis (Condensation)? * 7 How many Malonyl CoA? * 7 How many Acetyl CoA? * 1 How Many NADPH? * 14
7
Production of Cytosolic Acetyl CoA for FA Synthesis
Inner mitochondrial membrane is immpermiable to Acetyl CoA
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NADH NAD+
8
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