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Renin Angiotensin Mechanism.

De Novo Synthesis Of Fatty Acids (Palmitic Acid).

 

Definition:

  • De novo means new way of synthesis.

  • De novo synthesis of fatty acids is a set of processes that uses an acetyl CoA as a starting material to produce palmitic acid (Fatty Acids).

    • Typically, De novo Lipogenesis refers to the synthesis of fatty acids from acetyl-CoA, which is the beginning of de novo lipogenesis. 

    • Malonyl-CoA (3 carbons) is first created by removing acetyl-CoA from the mitochondria. 

    • An acetyl-CoA-malonic acid complex is produced when malonyl-CoA is combined with another acetyl-CoA. 

    • A 16-carbon fatty acid is formed by adding 2 carbons to carbons through a similar process 7 times.

Sites:

  • De novo synthesis mainly occurs in places like,

    • Liver,

    • Adipose tissue,

    • Kidneys.

De novo synthesis of fatty acids occurs in three stages:

  1. Production of acetyl CoA and NADPH

  2. Conversion of acetyl CoA to malonyl CoA

  3. Reactions of fatty acids synthase complex.

  1. Production of acetyl CoA and NADPH:

  • For fatty acids to be produced, acetyl CoA is essential. The main source of Acetyl CoA is pyruvate, which is oxidized in the mitochondrial matrix, as well as amino acids and ketone bodies.

  • To transport acetyl CoA, alternative arrangements must be made because it cannot penetrate mitochondrial membranes.

  • Oxaloacetate is formed from acetyl CoA, which is then condensed to acetyl CoA. Citrate is easily removed from the matrix and transported into the mitochondrial cytosol matrix.

  1. Conversion of acetyl CoA to malonyl CoA:

  • Malonyl CoA is produced by carboxylation acetyl CoA.

  • This is an ATP dependent reaction and requires biotin for CO2 fixation.

  1. Reactions of fatty acids synthase complex:

  • Reactions of fatty acid synthase are catalyzed by a multifunctional enzyme known as fatty acid synthase (FAS) complex.

  • Each monomer possesses the activity of a different enzyme and an acyl carrier protein (ACP).

  • This sequence of reactions is as  below.

  • Step 1a & 1b:

    • Fatty acid synthesis starts with the formation of acetyl ACP and malonyl ACP. 

    • The two enzymes involved respectively are acetyl transacylase and malonyl transacylase. In this case, acetyl CoA reacts with ACP to form acetyl ACP and coenzyme A (CoA). 

    • Malonyl CoA is reacted with ACP to form malonyl ACP and CoA. 

    • ACP is the acyl carrier protein. It is a protein that holds the growing fatty acid chain during its synthesis.

  • Step 2: 

    • A condensation reaction occurs between acetyl ACP and malonyl ACP to form acetoacetyl ACP. 

    • One of the acyl carrier proteins is released along with a molecule of carbon dioxide. 

    • Enzyme : acyl-malonyl ACP condensing enzyme.

  • Step 3: A reduction reaction

    • Acetoacetyl ACP is reduced to D-3-hydroxybutyryl ACP using NADPH as the reducing agent. 

    • Enzyme: beta-ketoacyl ACP reductase.

  • Step 4: A dehydration reaction

    • D-3-hydroxybutyryl ACP is dehydrated to generate crotonyl ACP otherwise known as trans-Δ2-enoyl ACP. 

    • Enzyme: 3-hydroxyacyl ACP dehydratase.

  • Step 5: The final step – a reduction reaction

    • In the final step, crotonyl ACP is reduced to butyryl ACP and NADPH is the reductant. 

    • Enzyme : enoyl ACP reductase. 

  • So we come to the end of the first elongation cycle but it is also the start of the first round of generating a fatty acid. 

The Second Round Of De Novo Synthesis Of Fatty Acids

  • In the second round of fatty acid synthesis, butyryl ACP condenses with another molecule of malonyl ACP to form C6-beta-ketoacyl ACP.

  • A repeat of steps 2 to 5 with reduction, dehydration and reduction again produces a C-6 acyl ACP that is then ready for a 3rd round of elongation.

Termination

  • If palmitic acid is the end product, then there are rounds of synthesis which produce a 16 carbon palmitoyl group (palmitoyl-ACP). 

  • This is hydrolysed using a thioesterase to generate palmitate whilst the ACP is returned to its original state with the sulfhydryl group where the fatty acid group used to be.

Summary:

  • There are 16 carbon atoms in palmitate, and 2 of these atoms come from Acetyl CoA, and the remaining 14 atoms come from Malonyl CoA. 

  • The overall reaction between palmitate and the body is summarized as follows:

Diagrammatic Representation:

Commonly Asked Questions:

  1. Explain in detail “ De Novo Synthesis Of Fatty Acids (Palmitic Acid)”.
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