Major Components and Sites of Fatty Acid Synthesis:-
1.Lipids as Stored Energy:
Lipids, which are considered a principal form of stored energy, are the major components of the phospholipid bilayer of the plasma membrane.
2.Sites of Fatty Acid Synthesis:
The liver, kidney, adipose tissue, and lactating mammary glands are the primary sites of fatty acid synthesis.
3.Site of Fatty Acid Biosynthesis:
Fatty acid biosynthesis occurs in the cytosol.
Prerequisites for Fatty Acid Biosynthesis:-
The prerequisites for fatty acid biosynthesis include the following components:
1.Acetyl CoA
2.NADPH
3.ATP
Stages of Fatty Acid Biosynthesis
Fatty acid biosynthesis can be understood in three stages:
1.Production of Acetyl CoA and NADPH:
💫Acetyl CoA is produced in the mitochondria by the oxidation of pyruvate and the oxidation of fatty acids.
💫The challenge is that for fatty acid biosynthesis, acetyl CoA must be transported from the mitochondria to the cytosol.
💫 This is achieved by the conversion of acetyl CoA to citrate, which can pass through the mitochondrial membrane. In the cytosol, citrate is cleaved back into acetyl CoA and oxaloacetate by the enzyme citrate lyase.
2.Conversion of Acetyl CoA to Malonyl CoA:
💫 Malonyl CoA is formed by the carboxylation of acetyl CoA by an enzyme called acetyl CoA carboxylase.
💫This enzyme is ATP-dependent and requires biotin as a cofactor.
3.Reactions Catalyzed by Fatty Acid Synthase Complex:
💫 This complex catalyzes a series of reactions that elongate the fatty acid chain.
Detailed Steps:—
1.Production of Acetyl CoA and NADPH:
💫 Acetyl CoA is produced in mitochondria by the oxidation of pyruvate and the oxidation of fatty acids.
💫 In mitochondria, acetyl CoA condenses with oxaloacetate (OAA) to form citrate. Citrate can pass through the mitochondrial membrane and, once in the cytosol, is cleaved by citrate lyase into OAA and acetyl CoA.
2.Formation of Malonyl CoA:
💫 Malonyl CoA is formed by the carboxylation of acetyl CoA by acetyl CoA carboxylase.
💫This enzyme requires ATP and biotin as a cofactor.
By understanding these stages and prerequisites, the process of fatty acid biosynthesis, specifically the biosynthesis of palmitic acid, can be comprehensively
Fatty Acid Synthesis
Reaction Catalyzed by Fatty Acid Synthase Complex:-
The reaction catalyzed by the Fatty Acid Synthase (FAS) complex forms a long-chain fatty acid called palmitic acid.
Steps Involved in Fatty Acid Synthesis:
STEP 1: Condensation Reaction
✓Description: The acetyl group from acetyl-CoA and the malonyl group from malonyl-CoA are transferred to the Fatty Acid Synthase complex by acetyl-CoA:ACP transacylase and malonyl-CoA:ACP transacylase.
✓Reaction: The acetyl group, which is the first acyl group, and the 2-carbon unit derived from malonyl-CoA extend the acyl chain by 2 carbons.
✓Product:β-Ketobutyryl-ACP.
✓Enzyme:β-Ketoacyl-ACP synthase.
✓Note:Decarboxylation occurs during this step.
STEP 2: Reduction Reaction
✓Description: β-Ketobutyryl-ACP undergoes a reduction reaction.
✓Electron Donor:NADPH.
✓Enzyme: β-Ketoacyl-ACP reductase.
✓Product: β-Hydroxybutyryl-ACP.
STEP 3: Dehydration Reaction
✓Description: β-Hydroxybutyryl-ACP undergoes dehydration.
✓Enzyme: β-Hydroxyacyl-ACP dehydratase.
✓Product: Butenoyl-ACP.
Note:Water is eliminated during this reaction.
STEP 4: Second Reduction Reaction
✓Description: Enoyl-ACP reductase catalyzes the reduction of butenoyl-ACP.
✓Electron Donor: NADPH.
✓Product: Acyl-ACP (specifically, butyryl-ACP).
✓Note: The acyl group attached to ACP is a 4-carbon unit (butyryl-ACP).
Chain Elongation:-
✓Process: The acyl-ACP (butyryl-ACP) transfers the carbon chain to the cysteine residue on the enzyme complex, repeating the above-mentioned reactions six more times to extend the fatty acid chain to 16 carbons, forming palmitic acid.
✓Summary: The fatty acid synthesis involves repeated cycles of condensation, reduction, dehydration, and reduction, ultimately leading to the formation of palmitic acid (a 16-carbon saturated fatty acid).
Synthesis of Palmitate
1.Repetitive Reactions for Palmitate Formation:-
💫Total of 7 cycles of reactions are required to form a 16-carbon palmitate molecule.
💫In each cycle, a chain of 18 carbons is elongated by 2 carbon atoms.
2.Final Step in Palmitate Formation:-
💫Finally, palmitoyl thioesterase separates palmitate from ACP, resulting in a fully saturated 16-carbon compound known as palmitate.
3.Overall Reaction:
💫The overall reaction for the synthesis of palmitate is as follows:
7 Acetyl-CoA + 7 CO₂ + 7 ATP + 7 malonyl-CoA + 7 ADP + 7 Pi + 14 NADPH + 14 H⁺ → Palmitate + 7 CO₂ + CoA + 14 NADP⁺ + 6 H₂O.
Regulation of Fatty Acid Synthesis
1.Control by Hormones, Enzymes, and Metabolites:
💫Fatty acid synthesis is regulated by hormones, enzymes, metabolites, and end products.
2.Acetyl-CoA Carboxylase:
💫The enzyme acetyl-CoA carboxylase is active in its polymeric form and inactive when it exists in a monomeric form.
3.Hormonal Control:
💫Involves cAMP-dependent phosphorylation, which inactivates the enzyme, and dephosphorylation, which activates it. Insulin promotes fatty acid synthesis, while glucagon inhibits it.
4.Availability of NADPH:
💫NADPH is provided by citrate (through Acetyl-CoA), significantly influencing fatty acid synthesis.
