Fatty Acid Biosynthesis

The cytosol is the primary site for lipogenesis or de novo synthesis of fatty acids. Many tissues, including the liver, mammary gland, kidney, brain, adipose tissues and lung, contain this system. Among its cofactor requirements are ATP, biotin, Mn, NADPH and HCO₃ (source of carbon dioxide). The immediate substrate is acetyl CoA, and the final product is free palmitate.

Table of Contents

• Steps Involved in Fatty Acid Synthesis
• Biomedical Significance of Fatty Acid Synthesis
• Frequently Asked Questions

Steps Involved in Fatty Acid Synthesis

• The first and foremost controlling step involved in the fatty acid biosynthesis is the production of malonyl-CoA.
• In the initial reaction, acetyl-CoA is carboxylated to malonyl-CoA in the presence of ATP and acetyl-CoA carboxylase, which calls for bicarbonate as a source of CO₂. This enzyme is crucial for controlling the synthesis of fatty acids.
• The fatty acid synthase (FAS) enzyme complex produces fatty acids following the synthesis of malonyl-CoA. This multienzyme polypeptide complex, which includes the acyl carrier protein (ACP), links the individual enzymes necessary for fatty acid synthesis.
• The multienzyme complex includes 4′-phosphopantetheine, a form of the vitamin pantothenic acid.
• Initially, a cysteine (-SH group) joins with an acetyl-CoA priming molecule, while malonyl-CoA joins with the -SH group next to it on the 4′-phosphopantetheine of ACP of the other monomer. Malonyl acetyl transacylase catalyses these reactions, resulting in the formation of the acetyl (acyl)-malonyl enzyme.
• With the help of 3-ketoacyl synthase, the acetyl group attacks the methylene group of the malonyl residue and releases CO₂ to create the 3-ketoacyl enzyme, which then releases the cysteine -SH group.
• Decarboxylation enables the reaction to proceed to completion, moving the entire chain of reactions forward.
• To create the corresponding saturated acyl-enzyme, the 3-ketoacyl group is first reduced, then dehydrated and reduced once more.
• The saturated acyl residue is transferred to the free cysteine -SH group when a new malonyl-CoA molecule joins with the -SH of 4′-phosphopantetheine.

Up until the formation of a saturated 16-carbon acyl radical (palmitoyl), the series of reactions is repeated six more times. Before the free palmitate can move along any other metabolic pathway, it must first be activated to acyl-CoA.

Palmitic Acid Synthesis

Palmitate contains a 16-carbon saturated fatty acid called palmitic acid which is the most common fatty acid found in palm oil.

Acetyl-CoA and malonyl-CoA are combined to form palmitate, as per the following equation:

CH₃CO-S-CoA (Acetyl CoA) + 7HOOCCHCO-S-CoA (7 Malonyl CoA) + 14NADPH + 14H⁺ → CH₃(CH₁₂)₁₄COOH (Palmitate) + 7CO₂ + 6H₂O + 8CoA-SH + 14NADP⁺

Do Check: MCQs on Biosynthesis

Biosynthesis of Long-chain Fatty Acids

Propionyl-CoA is used as the primer rather than acetyl-CoA.for the synthesis of long-chain fatty acids. Especially for fatty acids with an odd number of carbon atoms, which are found primarily in ruminant milk and fat.

Biomedical Significance of Fatty Acid Synthesis

The entire synthesis of palmitate from acetyl-CoA in the cytosol is accomplished by an extramitochondrial system. This extramitochondrial system produces fatty acids.

Most mammals use glucose as their main substrate for lipogenesis, but ruminants use acetate as their main dietary source of fuel. Type 1 (insulin-dependent) diabetes mellitus inhibits lipogenesis, and changes in the process’s activity have an impact on the type and extent of obesity. The phospholipids in the cell membrane play a crucial role in maintaining the fluidity of the membrane. It is thought that a diet with a high polyunsaturated fatty acid to the saturated fatty acid ratio (P:S ratio) will help prevent coronary heart disease.

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