Fatty Acid Synthesis

Hello :) This post will cover the process of fatty acid synthesis or lipogenesis. We'll look at the function, regulation and special features of lipogenesis. Enjoy!

Lipogenesis

The function of lipogenesis is to synthesis long chain fatty acids which are the major store of energy in animals. Fatty acid synthesis occurs in the cytosol of the cells in all tissues. However, there are a few key places where lipogenesis occurs, this includes: the liver, adipose tissue and mammary glands. Lipogenesis essentially 'strings' together 16 CH2 groups together to form palmitic acid. The pathway gets its carbon from acetylCoA and its hydrogen atoms from NADPH. Lipogenesis occurs through the citrate cleavage pathway which is shown below:

The Citrate Cleavage Pathway

There are several key steps involved. Firstly, acetylCoA is created from glucose through glycolysis as well as through the citrate cleavage pathway where citrate is converted to oxaloacetate and acetylCoA by ATP citrate lyase. Oxaloacetate is converted to malate and then to pyruvate by NADP malate dehydrogenase. This involves the conversion of NADP to NADPH. AcetylCoA is then converted to malonylCoA and then to NEFACoA which is assembled into a fatty acid. This requires NADPH, half of which comes from the conversion of oxaloacetate to malate, the other half comes from the Pentose Phosphate Pathway.   

This pathway is regulated by several things:

• Supply of substrate: the more glucose is available, the more fatty acids can be synthesised. 
• Endocrine regulation of activity by covalent modification: Insulin stimulates the pathway while glucagon, adrenaline, ACTH and Growth Hormone inhibit the pathway. AcetylCoA carboxylase is also activated through dephosphorylation by Insulin. The pathway is also allosterically activated by citrate and inhibited by NEFACoA.
• Endocrine regulation by enzyme expression: Insulin causes an increased synthesis of NADP malate dehydrogenase, ATP citrate lyase, acetylCoA carboxylase and fatty acid synthase. 

 

Ruminanats:

In ruminants, however, their fatty acids are synthesised from acetate. In order to do this they have some special features: they get their carbon source for this reaction from acetate. Acetate is also their source of NADPH via NADP isocitrate dehydrogenase found in the cytosol. 50% of their NADPH is derived from the Pentose Phosphate Pathway, the other 50% comes from the cytosolic NADP isocitrate dehydrogenase. This is inhibited by high levels of NEFACoA and stimulated by high levels of acetate. It is also regulated at the acetylCoA carboxylase step by the same mechanisms described above for non-ruminants.

 

That's all for this post, if you have any questions please feel free to ask :)