Biosnthesis of fatty acid

1. A
Presentation on
Biosynthesis of Fatty acid
Course title: Principle of Plant
Physiology
Submitted to:
Dr. H.S. Bhadauria;
Submitted by:
Gami Pankajkumar B.
M.Sc.(Agri.)GPB 1st sem,
1

2. Introduction:
 Fatty acid consists of a straight chain of an
even number of carbon atoms, with hydrogen
atoms along the length of the chain at one end
and a carboxyl group (―COOH) at the other
end. It is that carboxyl group that makes it an
acid (carboxylic acid).

3. They are the simplest form of lipids.
Occurrence:
Fattyacids mainly occur in the esterified form as
major constituents of various lipids.
 They are also present as free (unesterified) fatty
acids.
Fatty acids of animal orgin are much simpler in
structure in contrast to those of plant origin which
often contain groups such as epoxy, keto, hydroxy
and cyclopentane rings.

4. Even and odd carbon fatty acids:
Most of the fatty acids that occur in natural
lipids are of even carbons (usually 14C-2OC).
This is due to the fact that biosynthesis of fatty
acids mainly occurs with the sequential addition
of 2 carbon units.
 Palmitic acid (l6C) and stearic acid (l8C) are
the most common.
 Among the odd chain fatty acids, propionic
acid (3C) and valeric acid (5C) are well known.

5. Saturated and unsaturated fatty acids:
Saturated fatty acids do not contain double bonds,
while unsaturated fatty acids contain one or more
double bonds.
 Both saturated and unsaturated fatty acids almost
equally occur in the natural lipids.
 Fatty acids with one double bond are
monounsaturated and those with 2 or more double
bonds are collectively known as polyunsaturated fatty
acids (PIJFA).

6. De novo synthesis of fatty acids:
The production of carbohydrates and amino acids by
the mesophyll cells is primarily destined for export to
other parts of the plants, the synthesis of fatty acids
occurs only for the cell’s own requirements, except in
seeds and fruits.
Plants are not capable of long distance fatty acid
transport. Since fatty acids are present as constituents
of membrane lipids in every cell, each cell must
contain the enzymes for the synthesis of membrane
lipids and thus also for the synthesis of fatty acids.
In plants the de novo synthesis of fatty acids always
occurs in the plastids: in the chloroplasts of green cells
and the leucoplasts and chromoplasts of non-green
cells.

7. Although in plant cells enzymes of fatty acid
synthesis are also found in the membrane of the ER,
these enzymes appear to be involved only in the
modification of fatty acids, which have been
synthesized earlier in the plastids.
Oxidation of fatty acid leades to the formation of
acetyl CoA molecules and it is natural expect that
reversal of the oxidative pathway might lead to the
synthesis of fatty acid.
Truth is that fatty acids are synthesized from acetyl
CoA , but synthesis does not occur by reversal of
oxidative pathway .
Biosynthesis of fatty acid is an energy requiring
process.

8.  Enzyme and cofactor involved in synthesis
of fatty acid:
Acetyl Co A carboxylase
Fatty acid Synthase
Both the enzymes are multienzyme complexes
 Coenzymes and cofactors are-
Biotin
NADPH
Mn++
Mg++
And also ATP ,Acetyl CoA

9. Localization

10.  The creation of fatty acid from Acetyl
CoA and malonyl CoA through enzyme
process is known as fatty acid synthesis.
 In 1945 David Rittenberg and Konrad
Bloch demonstrated through isotopic
labelling techniques.
 In 1950 Sahil Wakil discovered a requirement
for bio carbonate in fatty acid biosynthesis and
malonyl-CoA was shown to be an intermediate.
Biosynthesis of fatty acid:

11.  In vertebrates its happen into cytosol
but in plant and bacteria its occur into
chloroplast.
 The pathway of biosynthesis is not
exactly reverse as β oxidation.
 Fatty acid breakdown and biosynthesis
occur into different compartments of cells,
catalysed by different pathways &
catalysed by different enzymes.

12. Acetyl CoA is a precursor for the synthesis of
fatty acids
Acetyl CoA is provided in different ways. Like
mitochondria , plastids which contain a pyruvate
dehydrogenase complex, by which pyruvate is
oxidized to acetyl CoA, accompanied by the
reduction of NAD+.
 In chloroplasts, however, depending on the
developmental state of the cells, the activity of
pyruvate dehydrogenase is often low. On the other
hand, chloroplasts contain a high activity of acetyl
CoA synthetase, which can convert acetate upon
consumption of ATP to acetyl CoA.

14. Source of NADPH:
In chloroplasts, photosynthesis provides the
NADPH required for the synthesis of fatty acids.
In leucoplasts, the NADPH required for fatty acid
synthesis is provided by the oxidation of glucose
6-phosphate via the oxidative pentose phosphate
pathway .

15. Formation of Malonyl-CoA: Committed Step
Enzyme: Acetyl‐CoA Carboxylase
Fatty acid synthesis starts with the carboxylation of acetyl
CoA to malonyl CoA by acetyl CoA carboxylase, with
the consumption of ATP .

16. Acetyl CoA carboxylase is the first enzyme of fatty acid
synthesis
The carboxylation of acetyl CoA involves biotin which
acts as a carrier for “activated CO2” .
Biotin is covalently linked with its carboxyl group.
This reaction is driven by the hydrolysis of ATP.
Therefore the acetyl CoA carboxylation requires two steps:
1. Biotin is carboxylated at the expense of ATP by biotin
carboxylase.
2. Bicarbonate is transferred to acetyl CoA by carboxyl
transferase.

18. All three proteins—the biotin carboxyl carrier protein,
biotin carboxylase, and carboxyl transferase—form a single
multienzyme complex.
The biotin is attached to the carrier protein by a long
flexible hydrocarbon chain, it reacts alternately with the
carboxylase and carboxyl transferase in this multienzyme
complex.
Acetyl CoA carboxylase, the first enzyme of fatty acid
synthesis, is an important regulatory enzyme and its
reaction is regarded as a rate-limiting step in fatty acid
synthesis.

19. In chloroplasts, the enzyme is fully active only
during illumination and is inhibited during darkness.
This ensures that fatty acid synthesis proceeds mainly
during the day, when photosynthesis provides the
necessary NADPH.
The mechanism of light regulation is similar to the light
activation of the enzymes of the Calvin cycle :
The acetyl CoA carboxylase is reductively activated by
thioredoxin and the activity is further enhanced by the
increase of the pH and the Mg++ concentration in the
stroma.
Further steps of fatty acid synthesis are also catalyzed
by a multienzyme complex

20. Activation
 Fatty acid synthesis starts with the formation of acetyl
ACP and malonyl ACP.
 Acetyl transacylase and malonyl transacylase
catalyze these reactions.

21. In a subsequent reaction, CoA is exchanged by acyl
carrier protein (ACP) . ACP comprises a serine
residue to which a pantetheine is linked via a
phosphate group.The pantetheine is also a functional
constituent of CoA.
After formation of this acetyl ACP and malonyl ACP
the long chain fatty acid is then synthesized in
repetition of 4 stage sequence.
1.Condentation.
2. reduction-l
3. Dehydration.
4.Reduction-ll
In each cycle of 4 step the fatty acid is extended by 2
carbon chain.
All the process was catalysed by complex of enzyme
called as fatty acid synthas.

22.  First domain or Condensing unit:
 It is initial substrate binding site.
 The enzymes involved are β-keto acyl synthase or
condensing enzyme (CE), acetyl transferase (AT) &
malonyl transacylase (MT).

23.  It contains the dehydratase (DH), enoyl reductase
(ER), β-keto acyl reductase (KR) & acyl carrier
protein (ACP)
 The acyl carrier protein is a polypeptide chain
having a phospho-pantotheine group, to which
acyl groups are attached in thioester linkage.
 ACP acts like CoA carrying fatty acyl groups.

24.  It is involved in the release of synthesized fatty
acid in the cytosol.
 Major fatty acid synthesized is palmitic acid.
 It contains thio-esterase(TE) or de-acylase.
 Eukaryotes - ACP is a part of FAS complex
 Prokaryotes – FAS complex + separate acyl carrier
protein

25. Advantages of Multi-enzyme Complex:
Intermediates of the reaction can easily interact with
the active sites of the enzymes.
 One gene codes all the enzymes; all
enzymes
 All are in equimolecular
concentrations.
 The efficiency of the process is enhanced.

27. Condensation reaction-
Acetyl ACP and malonyl
ACP react to form
acetoacetyl ACP.
Enzyme - β-keto acyl
ACP synthase enzyme.

28. Reduction 1reaction-
Acetoacetyl ACP is
reduced to
D 3-hydroxybutyryl
ACP.
NADPH is the
reducing agent
Enzyme: β-ketoacyl
ACP reductase

29. Dehydration Reaction-
D-3-hydroxybutyryl ACP is
dehydrated to form
crotonyl ACP.
Enzyme:
β-hydroxyacyl ACP
dehydratase

30. Reduction 2 reaction-
 The final step in the cycle
reduces crotonyl ACP to butyryl
ACP.
 NADPH is reductant.
 Enzyme - enoyl ACP
reductase.
 This is the end of first
elongation cycle (first round).

31. In the second round
butyryl ACP condenses with
malonyl ACP to form a C6-
 -ketoacyl ACP.
Reduction, dehydration, and
a second reduction convert
the C6-  - ketoacyl ACP into
a C6- acyl ACP, which is
ready for a third round of
elongation.

32. Termination:
• Rounds of synthesis continue until a C16
palmitoyl group isformed ( 6 time repeat)
• Palmitoyl-ACP is hydrolyzed by a
thioesterase

33. The overall reaction for the synthesis of
palmitate from acetyl-CoA can be considerd in
two parts.
First, the formation of seven malonyl-CoA
molecules:
7 Acetyl-CoA + 7CO2 + 7ATP 7 malonyl CoA + 7ADP +
7Pi

34. Then the seven cycles of condensation and reduction
Acetyl-CoA + 7malonyl-CoA + 14NADPH + 7ATP
palmitate + 7CO2 + 8CoA +7ADP + 7Pi + 14NADP+
The biosynthesis of FAs requires acetyl-CoA and the
input of energy in the form of ATP and reducing power
of NADPH.

35. Reference:
Textbook of Biochemistry-U Satyanarayana
Textbook of Biochemistry-DM Vasudevan
Biochemistry- Lehninger
Plant Biochemistry by Hans-Walter Heldt &
Birgit Piechulla