Fatty acids and their biosynthesis

1. Fatty acids and their biosynthesis

2. Fatty Acids
• Unbranched long chain compounds with carboxylic acid functionality
• Most naturally occurring fatty acids have even number of C atoms
• They are found only in trace amounts in living cells their free,
unesterified form
CH3CH2(CH2CH2)n CH2 COOH

3. Fatty Acids
CH3CH2(CH2CH2)n CH2 COOH
Number of C
atoms
n Fatty acid
[Trivial name ]
Systematic name
C4 0 Butyric acid n-Butanoic acid
C6 1 Caproic acid n-Hexanoic acid
C8 2 Caprylic acid n-Octanoic acid
C10 3 Capric acid n-Decanoic acid
C12 4 Lauric acid n-Dodecanoic acid
C14 5 Myristic acid n-Tetradecanoic acid
C16 6 Palmitic acid n-Hexadecanoic acid
C18 7 Stearic acid n-Octadeconoic acid

4. Fatty Acids
• Fatty acids with chain length greater than C 20 is rare.
The lower acids occur mainly in animal fats
• Cows milk contains considerable amount of beutanoic acid
• Fatty acids occur in living system in various form.
• . Waxes and Glycerides
O
R (CH2)n O -(CH2)n -R
Bee wax C24-C26 Fatty acid + C28-C30
Alcohol

5. Fatty Acids
• Ubiquitous
• Play a vital role in life
• Energy production
• Component in cellular structure
• More uncommon fatty acids are considered to as
secondary metabolites.
Primary metabolites

6. Fatty Acids
Energy production
• They can be broken down to acetyl Co A which can
enter the citric acid cycle to give energy (b oxidation)
• b oxidation occurs at the inner membrane of the
mitochondria
.

7. Carnitine Shuttle
long-chain fatty acid molecules are impermeable to the mitochondrial membranes
carnitine shuttle involves in transporting these impermeable molecules into mitochondria matrix for β-oxidation

8. Free fatty acid
(in blood)
Albumin bound
fatty acid
Albumin bound
fatty acid
Free fatty acid
(in cytoplasm)
carnitine bound
fatty acid
(Acyl carnitine)
Acyl CoA
Cytoplasm Mitochondria
matrix
Acetyl Co A
β Oxidation
Mitochondria inner
membrane
Carnitine
Acyl carnitine

9. b oxidation
R OH
O
R
C
SCOA
O
R
C
SCOA
O
O
H
C C
SCOA
O
R
H
R
C C
SCOA
O
O
COASH
..
R
C
SCOA
O
C
H3
C
O
SCOA
+

11. Biosynthesis of fatty acids
• Start with acetyl co A
• CO2 or HCO3- is essential
• Studies with labeled CO2 have shown that CO2 is not incorporated in
to fatty acid.
• Acetyl co enzyme A first converted in to malonyl-coenzyme A via
carboxilation
• The cofactor Biotin and associated Biotin Carboxyl carrier Protein
(BCCP) are involved in this process.
(Malonyl CoA is a more powerful nucleophile than acetyl CoA).

12. S
N
H NH
O
BCCP
O
S
N
H N
O
–
BCCP
O
ATP
P P adenosine
H2O
..
C O
O
S
N
H N
O
BCCP
O
O
–
O
+ ADP
S
N
H N
O
BCCP
O
O
–
O
ACOS
O
H
H
H
Enzyme --X
-
O
–
SCOA
O O
Malonyl SCOA
CH4

13. C
H3 SCoA
O
ACP -SH
C
H3 S - ACP
O
O
- SCoA
O O
ACP -SH
O
- S - ACP
O O
O
- S - ACP
O O
C
H3 S - E
O
CO2
C
H3 S - ACP
O O
N
H
H
R
NH2
O
R
s
NADPH, H
+
Acetoacetyl ACP
C
H
O
H
C
H3 C
H
C
H
S -ACP
O
Syn elimination of H2O molecule
C
H3 S -ACP
O
H
H
NADPH, H
+
C
H3 S -ACP
O
C
H3 S - ACP
O
C
H3 S - E
O
+ CO2 + E -SH
E -SH
( b -ketoacyl - ACP synthatase)

14. Biosynthesis of fatty acids
• Saturated thioester grows as in above until it reaches around C-14 or
C-18 , then it is released from the enzyme.
C
H3 S -ACP
O
S -ACP
O
C
H3

15. • The usual starter of biosynthesis of fatty acid is Acetyl
CoA. But some times different startes may be involved
C
H3
SCoA
O
CH3CH2(CH2CH2)7 COOH
C -17 Odd number of C atoms
Propyl group
C
H3
CH3
SCoA
O
Isobytanyl
(CH3)2CH(CH 2CH2)7COOH
SCoA
O
Eg. Bacillus acidocaldarious

16. Unsaturated fatty acids
H3C(H2C)7
H H
(CH2)7COOH
Oleic acid - [18 C]
(CH2)7 COOH
H3C(H2C)4
Skipped double bond system
Linoleic acid
H3C(H2C)4
COOH
Arachidonic acid

17. Unsaturated fatty acids
• Animal fats are generally high in saturated fatty acids
but vegetable oil have high % of unsaturated fatty
acids
• Arachidonic acid is found in mammalian adrenal
glands
• Commercially most important reaction of unsaturated
fatty acids is auto-oxidation by atmospheric oxygen
that leads rancidity. This can be prevented by adding
antioxidants

18. Biosynthesis of Unsaturated fatty acids
• Biosynthesis of unsaturated fatty acids arises by
the desaturation of the saturated fatty acids
• Two pathways are known for the introduction of
double bond in to these saturated fatty acids.
• Aerobic route
• Anaerobic route

19. Aerobic pathway
• Aerobic organisms (plants, and mammals, aerobic
bacteria etc)
CH3 (CH2)7
H
(CH2)7
H
S -X
O
S S
CH3 (CH2)7
H
(CH2)7
H
S -X
O
+
SH SH

20. Anaerobic pathway
H13C6
OH
H H
H
SX
O
 

Syn elimination
H13C6
SX
O
H H
H
-
H13C6
H H SX
O
H13C6 (CH2)9
O
H

21. • Uncommon /rare fatty acids – secondary metabolites
• Eg. Insect pheromones
• Sex pheromones -Sexual attraction in insects is mainly
controlled by sex pheromones. Communication through
pheromones plays an important role in signaling the readiness
to mate between sexually mature individuals.
• Alarm Pheromones
When there is a danger insects release alarm pheromones and
warn others.
• Eg Atta texana (an ant species)

22. Arachidonic acid
• C-20 unsaturated fatty acid
• precursor of important prostaglandin hormones
• first detected in seminal plasma
• biosynthesized from oleic acid.
COOH
CH3

23. Prostaglandins
• The existence of prostaglandin was first noted in1930,
by two gynecologists
• some unidentified substances in human semen -
would cause smooth muscle to contract
-lower the blood pressure of animals
• people believed that these compounds are derived
from prostate glands.
Named as prostaglandin
• widely distributed in animal tissues

24. COOH
CH3
O
O
COOH
CH3
O
O
O
O
.
- e
+ H
+
COOH
CH3
O
O
HOO
O
O
COOH
CH3
O
H
COOH
CH3
O
O
HOO
COOH
CH3
O
H
O
H
O
H
PGG2
Thromboxane A2
[H]
PGG2
PGF2 

25. COOH
CH3
O
O
HOO
PGG2
O
COOH
O
H
CH3
O
H
[H]
PGI2 Prostacyclin

26. PGI2 and TXA2
• PGI2 has enol-ether functionality. Enol-ethers are very unstable at acidic
condition.
• PGI2 and TXA2 involve in the control of agglutination of blood platelets
• PGI2 Prevent agglutination
• TXA2 causes agglutination
• Important in the treatment of Arterial diseases and prevention of thrombosis.

27. PGE 1 and PGE2
• PGE 1 and PGE2 can be used to induce abortion
[first and second trimesters of pregnancy].
• Implicated in the normal functioning of the respiratory system
• Have an essential role in the control of blood pressure and they may have a
therapeutic potential as anti hypertensive agents
• Effective in decreasing gastric secretion.
• damaging effect of aspirin on the stomach may be due to its ability to inhibit
the biosynthesis of prostaglandin

28. Leukotriens