Lipogenesis(denovo synthesis of fatty acidds)

Fatty acid synthesis and regulation

2. 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.

3. Glucose Pyruvate
 Fatty acid oxidation
 Ketone bodies Acetyl CoA
 Amino acids

4.  HMP Shunt
Malic enzyme
Malate Pyruvate
NADP+ NADPH + H+

5. 1.Transport of acetyl CoA
2. Formation of Malonyl CoA
3. Reactions catalyzed by fatty acid synthetase
complex.

6. Fatty acid/Pyruvate/amino acid












Citrate
Synthase
Citrate
transporter
Transporte
r
Transporter
Malic
enzyme
Malic
enzyme
Acetyl CoA
Acetyl CoA
Citrate Lyase
MITICHONDRIA CYTOSOL
Oxaloacetate
Citrate
Citrate
Oxaloacetate
Malate
PyruvatePyruvate
Malate
NADH
NAD
NADP
NADPH
NADPH
NADPH
NADH
NAD
ATP ADP+Pi
Fatty acid Synthesis

7. Acetyl CoA carboxylase is rate limiting
enzyme.
Biotin is cofactor of the enzyme which is non-
covalently bond to enzyme.
Acetyl CoA Carboxylase
Acetyl CoA + CO2 Malonyl CoA
ATP Biotin ADP + Pi

8. 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.

9. De-
C
ond
ensing
U
nit
R
e
d
u
c
i
n
g

u
n
i
t
Releasing
unit
Enoyl
reductase
Dehydratase
Dehydratase
Enoyl
reductase

10. KS
AT
ER
DH
KR
ACP
TE
MT
TE
ACP
KR
DH MT
AT
KS
ER
Subunit Division
F
U
N
C
T
I
O
N
A
L
Cys
SH
SH
4’phospho
pantetheine
SH
Cys
4’phospho
pantetheine
SH
A

18. ß-Hydroxyacyl-C0A ß-Hydroxyacyl-ACP
Mitochondria Cytosol

19.  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

20. 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.

21. 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.

22. Short term regulation
1. Allosteric regulation
2.Covalent modification
Long term regulation
1.Hormonal regulation
2.Dietary regulation Induction/Repression

23. Citrate
Acetyl CoA
Malonyl CoA
Palmitic acid
Acetyl CoA
Carboxylase
+
-

24. Acetyl CoA
Carboxylase
(Active)
Acetyl CoA
Carboxylase
(Inactive)
Insulin
+
Protein Phoshatase
P
Glucagon/ Epinephrine
+
ATPADP
Pi
Protein kinase
Covalent modification

25. High Carbohydrate Diet
Low Fat Diet
Insulin
(induction)
Synthesis of all enzymes of
fatty acid biosynthesis
(repression)
High Fat Diet
Glucagon
Low Carbohydrate Diet
+
-