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Chapter: Biochemistry: Lipid Metabolism

Biosynthesis of fatty acids

Biosynthesis of fatty acids occurs in all organisms and in mammals it occurs mainly in adipose tissue, mammary glands, and liver.

Biosynthesis of fatty acids

1.           Biosynthesis of fatty acids occurs in all organisms and in mammals it occurs mainly in adipose tissue, mammary glands, and liver.

2.           Fatty acid synthesis takes place in the cytosol in two steps.

·              Formation of medium chain fatty acid of chain length 16 carbon atoms.

·              Lengthening of this carbon chain in microsomes for larger fatty acids.

3.           Acetyl CoA serves as a source of carbon atoms for saturated as well as unsaturated fatty acids. Acetyl CoA can be formed from excessive dietary glucose and glucogenic amino acids (amino acids which can be converted to glucose). Carbohydrates and aminoacids in the presence of oxygen is converted to pyruvate which inturn can be converted to acetyl CoA


The synthesis of fatty acid from acetyl CoA takes place with aid of a multi-enzyme complex termed as fatty acid synthetase complex. Palmitic acid is the major product of the fatty acids synthetase complex mediated reaction and hence it is also called as palmitate synthetase. It is a dimer with two identical subunits namely subunit-1 and subunit-2 arranged in a head to tail fashion. Each monomer of this enzyme complex contains seven enzymes; of these, each is assigned a definite function.

Migration of Acetyl CoA for the bio synthesis of Fatty acids

Formation of acetyl CoA from pyruvate takes place in mitochondria. Mitochondrial membrane is impermeable to acetyl CoA. Migration of acetyl CoA from the mitochondria to the cytoplasm is facilitated by the condensation of the acetyl CoA with oxaloacetate to form citrate which is permeable to mitochondrial membrane. In the cytoplasm, citrate readily decomposed back to acetyl CoA and oxaloacetate in the presence of ATP and co-enzyme A by the action of an enzyme called ATP - Citrate lyase.


Conversion of Acetyl CoA to Malonyl CoA

The acetyl - CoA is carboxylated in the cytoplasm in the presence of acetyl CoA carboxylase, a vitamin Biotin containing enzyme, which helps in carbondioxide fixation. Acetyl CoA carboxylase is the regulatory enzyme in the fatty acid biosynthesis.


Conversion of malonyl CoA to palmitic acid


The malonyl CoA is converted to palmitic acid by several steps and each of these steps are catalysed by different enzymes of fatty acid synthetase complex.

Acetyl CoA and malonyl CoA condenses to form butyryl-ACP with the formation of intermediates. This cycle repeats itself six times and in each cycle two carbon atoms (malonyl CoA) is added to butyryl ACP, ultimately resulting in the formation of palmitoyl CoA, a 16 carbon molecule.

 

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