1. Biosynthesis of Fatty Acid
*Prepared By*
Mr. Ansari Altamash Shakeel Ahmad
Assistant Professor
Y. B. Chavan College of Pharmacy, Aurangabad
Contact No:

2. Biosynthesis of Fatty Acid
Introduction
Reactions
Pathways
Fatty acid Synthase
Regulation
Reference
By: Altamash Ansari

3. Introduction
The dietary carbohydrates and amino acids, when consumed in excess, can be converted to fatty acids and stored as triacylglycerol's.
De novo (new) synthesis of fatty acids occurs predominantly in liver, kidney, adipose tissue and lactating mammary glands.
The enzyme machinery for fatty acid production is located in the cytosomal fraction of the cell.
Acetyl CoA is the source of carbon atoms while NADPH provides the reducing equivalents and ATP supplies energy for fatty acid formation.
By: Altamash Ansari

4. Reactions The fatty acid synthesis may be completed in 3 stages
Production of acetyl CoA and NADPH
Conversion of acetyl CoA to malonyl CoA
Reactions of fatty acid synthase complex.
By: Altamash Ansari

5. 1. Production of acetyl CoA and NADPH
Acetyl CoA is the starting material for de novo synthesis of fatty acids.
Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate, fatty acids, degradation of carbon skeleton of certain amino acids & from ketone bodies.
Mitochondria are not permeable to acetyl CoA.
An alternate or a bypass arrangement is made for the transfer of acetyl CoA to cytosol.
Acetyl CoA condenses with oxaloacetate in mitochondria to form citrate.
Citrate is freely transported to cytosol by tricarboxylic acid transporter.
By: Altamash Ansari

6. Oxaloacetate in the cytosol is converted to malate.
In cytosol it is cleaved by ATP citrate lyase to liberate acetyl CoA & oxaloacetate.
Oxaloacetate in the cytosol is converted to malate.
Malic enzyme converts malate to pyruvate.
NADPH & CO2 are generated in this reaction.
Both of them are utilized for fatty acid synthesis
By: Altamash Ansari

7. Transfer of acetyl CoA from mitochondria to cytosol
HMP Shunt
Glucose
Mitochondrial matrix
Cytosol
Pyruvate
Pyruvate
NADPH + H+
CO2
Malic enzyme
PDH Complex
Pyruvate
carboxylase
NADP+
Malate
Amino acids FA
NAD+
Fatty acid
MDH
NADH + H+
Oxaloacetate
Oxaloacetate
Acetyl CoA
ADP+Pi
Citrate lyase
Acetyl CoA
Citrate
synthase
ATP
CoASH
Citrate
Citrate
By: Altamash Ansari

8. 2. Conversion of acetyl CoA to malonyl CoA
Acetyl CoA is carboxylated to malonyl CoA by the enzyme acetyl CoA carboxylase.
This is an ATP-dependent reaction & requires biotin for CO2 fixation.
The mechanism of action of acetyl CoA carboxylase is similar to that of pyruvate carboxylase.
Acetyl CoA carboxylase is a regulatory enzyme
By: Altamash Ansari

9. Conversion of acetyl CoA to malonyl CoA
CH3 – C – SCoA
Acety CoA
CO2, ATP
Acetyl CoA carboxylase
Biotin
ADP + Pi O
-OOC – CH2 – C – SCoA
Malonyl CoA
By: Altamash Ansari

10. 3. Reactions of fatty acid synthase complex.
The remaining reactions of fatty acid synthesis are catalysed by a multifunctional enzyme known as fatty acid synthase (FAS) complex.
In eukaryotic cells, fatty acid synthase exists as a dimer with two identical units.
Each monomer possesses the activities of seven different enzymes & an acyl carrier protein (ACP) bound to 4'-phosphopantetheine.
Fatty acid synthase functions as a single unit catalysing all the seven reactions.
In Multifunction enzyme, Intermediates of the reaction can easily interact with the active sites of the enzymes.
By: Altamash Ansari

11. The efficiency of the process is enhanced.
The sequence of reactions of the extra mitochondrial synthesis of fatty acids (palmitate) is as follows
By: Altamash Ansari

12. Biosynthesis of long chain fatty acid-palmitate
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13. Biosynthesis of long chain fatty acid-palmitate
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14. Fatty acid synthase complex
It is a multienzyme complex
Fatty acid synthase is a dimer composed of two identical subunits (monomers),
Each with a molecular weight of 240,000.
Each subunit contains the activities of 7 enzymes of FAS & an ACP with 4'-phosphopantetheine SH group.
The two subunits lie in anti-parallel (head to tail) orientation
By: Altamash Ansari

15. Fatty acid synthase - multienzyme complex
Dehydratase
Enoyl
reductase
Ketoacyl
ACP
- Thioesterase
Ketoacyl
synthase
Acetyl
transacylase
Malonyl
4’-Phosphopantetheine I
Cys SH SH
Functional division
Subunit division SH SH I
Cys
4’-Phosphopantetheine
Ketoacyl
synthase
Acetyl
transacylase
Malonyl
Dehydratase
Enoyl
reductase
Ketoacyl
ACP
Thioesterase -
By: Altamash Ansari

16. Only the dimer is functionally active.
The -SH group of phosphopantetheine of one subunit is in close proximity to the -SH of cysteine residue (of the enzyme ketoacyl synthase) of the other subunit.
Each monomer of FAS contains all the enzyme activities of fatty acid synthesis.
Only the dimer is functionally active.
By: Altamash Ansari

17. FAS structure has both functional division & subunit division
The functional unit consists of half of each subunit interacting with the complementary half of the other.
FAS structure has both functional division & subunit division
The two functional subunits of FAS independently operate & synthesize two fatty acids simultaneously
By: Altamash Ansari

18. Significance of FAS complex
The FAS complex offers great efficiency that is free from interference of other cellular reactions for the synthesis of fatty acids.
There is a good coordination in the synthesis of all enzymes of the FAS complex.
By: Altamash Ansari

19. Regulation of fatty acid synthesis
Fatty acid production is controlled by enzymes, metabolites, end products, hormones and dietary manipulations.
Acetyl CoA carboxylase:
This enzyme controls a committed step in fatty acid synthesis.
By: Altamash Ansari

20. Citrate promotes polymer formation & increases fatty acid synthesis.
Acetyl CoA carboxylase exists as an inactive protomer (monomer) or an active polymer.
Citrate promotes polymer formation & increases fatty acid synthesis.
Palmitoyl CoA & malonyl CoA cause depolymerization of the enzyme, inhibits the fatty acid synthesis.
By: Altamash Ansari

21. Reference Textbook of Biochemistry-U Satyanarayana
Textbook of Biochemistry-DM Vasudevan
By: Altamash Ansari

22. Thank you
By: Altamash Ansari