Bio Chemistry

BIOCHEMISTRY 3(2+1)

Lesson 22 : Fatty Acid Synthesis

The Design Strategy for Fatty Acid Biosynthesis

1. Fatty acids are constructed by the addition of two carbon units derived from acetyl-CoA.
2. The acetate units are activated by the formation of malonyl-CoA at the expense of ATP.
3. The driving force for the addition of two carbon units to the growing chain is the decarboxylation of malonyl-CoA.
4. The chain elongation stops at palmitoyl-CoA.
5. Other enzymes add double bonds or additional carbon atom to the carbon chain of palmitoyl CoA for desatination or elongation.

Fatty acid biosynthesis in the cytosol requires a sufficient concentration of NADPH and acetyl-CoA.

NADPH is generated in the cytosol by the pentose phosphate pathway, and by the malic enzyme which oxidizes malate into pyruvate and CO2, generating NADPH.

There are 3 principle ways of producing acetyl-CoA in the cytosol of the cell.

• Amino acid degradation produces acetyl-CoA.
• Fatty acid oxidation in the matrix of the mitochondria produces acetyl-CoA
• Glycolysis also generates acetyl-COA

The acetyl-CoA formed by amino acid degradation is insufficient for fatty acid biosynthesis.

Acetyl CoA molecules are the building blocks of fatty acid synthesis. The acetyl CoA molecules need to be activated for fatty acid biosynthesis. Acetyl CoA is carboxylated to form malonyl CoA by acetyl CoA carboxylase which is a biotin containing enzyme. The carboxylation reaction is irreversible and is the first committed step of fatty acid biosynthesis.