Lipogenesis(denovo synthesis of fatty acidds)
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Transcript of Lipogenesis(denovo synthesis of fatty acidds)
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First discovered by Feodor Lynen. Also known as Lynen’s spiral.
It is not a reversal of oxidation. Cellular site: Cytoplasm Organ involved: Liver , kidney, adipose
tissue, brain and mammary gland. Immediate precursor: Acetyl CoA. Co-enzyme required: NADPH. The major fatty acid synthesized is
palmitic acid.
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Glucose Pyruvate Fatty acid oxidation Ketone bodies Acetyl CoA Amino acids
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HMP Shunt Malic enzyme Malate Pyruvate
NADP+ NADPH + H+
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1. Transport of acetyl CoA2. Formation of Malonyl CoA3. Reactions catalyzed by fatty acid
synthetase complex.
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Fatty acid/Pyruvate/amino acid
Citrate Synthase
Citrate transport
er
Transporter
Transporter
Malic enzymeMalic
enzyme
Acetyl CoA
Acetyl CoA
Citrate Lyase
MITICHONDRIA CYTOSOL
Oxaloacetate Citrate Citrate
Oxaloacetate
Malate
PyruvatePyruvate
Malate
NADHNAD
NADP
NADPHNADPH
NADPHNADH
NAD
ATP ADP+Pi
Fatty acid Synthesis
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Acetyl CoA carboxylase is rate limiting enzyme.
Biotin is cofactor of the enzyme which is non-covalently bond to enzyme.
Acetyl CoA CarboxylaseAcetyl CoA + CO2 Malonyl CoA ATP Biotin ADP + Pi
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The enzyme complex catalyzes the further steps of fatty acid synthesis.
It is a dimer consisting of 2 identical subunit. Each subunit consists of 7 different enzymes
and Acyl carrier protein(ACP). The SH group of 4’phosphopantetheine of
the ACP of one monomer is in close proximity to the SH group of cysteine residue of the ketoacyl synthase of other monomer.
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De-
Condensing
Unit
Reducing unit
Releasing unit
Enoyl reductase
Dehydratase
Dehydratase
Enoyl reductase
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KS
AT ERDH
KRACP TE
MT
TEACP
KRDH MT
AT
KS
ER
Subunit Division
FUNCTIONAL
CysSH
SH4’phospho pantethein
e
SHCys
4’phospho pantethein
eSH
A
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ß-Hydroxyacyl-C0A
ß-Hydroxyacyl-ACP
Mitochondria Cytosol
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Step2A: Transfer of the acetyl group to cysteinyl SH group of Ketoacyl synthase.
Step2B: Transfer of the Malonyl group to SH group of ACP.
Step3: Condensation of acetyl and malonyl group to from acetoacetyl-ACP.
Step4: Reduction Step5: Dehydration Step6: Reduction and formation of Butyryl-S-ACP
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Cycling of reactions: Butyryl group is transferred to the SH
group of condensing enzyme in other monomer. A molecule of Manonyl will bind to SH group of ACP in other monomer.
The sequence of reactions(3 to 6) are repeated 6 times for the synthesis of Palmitic acid(16C).
Tioesterase releases palmitate from multienzyme complex.
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Denovo synthesis of fatty acid in lactating mammary gland forms medium chain fatty acids{ Capric acid(10C) and Lauric acid(12C)}.
Palmitate is precursor for other long chain fatty acids.
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Short term regulation 1. Allosteric regulation 2.Covalent modificationLong term regulation1.Hormonal regulation 2.Dietary regulation Induction/Repression
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Citrate
Acetyl CoA
Malonyl CoA
Palmitic acid
Acetyl CoA Carboxylase
+
-
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Acetyl CoA Carboxylas
e(Active)
Acetyl CoA Carboxylase
(Inactive)
Insulin
+Protein Phoshatase
P
Glucagon/ Epinephrine
+ ATPADP
Pi
Protein kinase
Covalent modification
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High Carbohydrate
DietLow Fat Diet
Insulin(induction)
Synthesis of all enzymes of fatty acid biosynthesis
(repression)High Fat Diet
GlucagonLow Carbohydrate
Diet
+
-