fatty acid biosynthesis
Sunday 19 June 2005
Fatty acids are formed by the action of fatty acid synthases from acetyl-CoA and malonyl-CoA precursors.
Fatty acids are made by fatty acid synthases that polymerize and then reduce acetyl-CoA units.
The acyl chains in the fatty acids are extended by a cycle of reactions that add the acetyl group, reduce it to an alcohol, dehydrate it to an alkene group and then reduce it again to an alkane group.
The enzymes of fatty acid biosynthesis are divided into two groups, in animals and fungi all these fatty acid synthase reactions are carried out by a single multifunctional type I protein, while in plant plastids and bacteria separate type II enzymes perform each step in the pathway.
De Novo Synthesis in Humans
In humans fatty acids are predominantly formed in the liver and adipose tissue, and mammary glands during lactation.
Most acetyl-CoA is formed from pyruvate by pyruvate dehydrogenase in the mitochondria. Acetyl-CoA produced in the mitochondria is condensed with oxaloacetate to form citrate, which is then transported into the cytosol and broken down to yield acetyl-CoA and oxaloacetate by ATP-citrate lyase.
fatty acid elongation
Much like β-oxidation, elongation occurs via four recurring reactions shown below.
The first step is condensation of acetyl ACP and malonyl ACP. This results in the formation of acetoacetyl ACP. Although this reaction is thermodynamically unfavourable, the evolution of CO2 drives the reaction forward.
2. Reduction of acetoacetyl ACP
In this step, acetoacetyl ACP is reduced by NADPH into D-3-Hydroxybutyryl ACP. The double bond is reduced to a hydroxyl group. Only the D isomer is formed.
In this reaction, D-3-Hydroxybutyryl ACP is dehydrated to crotonyl ACP.
4. Reduction of crotonyl ACP
During this final step, crotonyl ACP is reduced by NADPH into butyryl ACP.
However, in animals these same reactions occur on a large dimeric protein, fatty acid synthase, which has the full complement of enzymatic activities required to synthesize and liberate a free fatty acid.
In the second step of elongation, butyryl ACP condenses with malonyl ACP to form an acyl ACP compound. This continues until a C16 acyl compound is formed, at which point it is hydrolyzed by a thioesterase into palmitate and ACP.
- anabolism (biosynthesis)