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Fatty Acid Synthesis
- Lipogenesis, the synthesis of fatty acids and their esterification to glycerol to form triacylglycerols, which occurs mainly in the liver in humans, with dietary carbohydrate as the major source of carbon.
- While the de novo synthesis of fatty acids from acetyl-CoA occurs in the cytosol on the fatty acid synthase complex.
- Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases.
Fatty acid synthesis takes place in the cytosol and is carried out by a multienzyme complex called FAS (fatty acid synthase complex).
Substrates (to make one palmitate):
- 8 acetyl CoA
- 14 NADPH
- 7 ATP
- 1 molecule of palmitate (16-carbon fatty acid)
- 7 H2O
Fatty Acid Synthesis Pathway
- Acetyl CoA is converted to malonyl CoA by acetyl CoA carboxylase.
- Malonyl CoA is transferred to FAS.
- Through a series of condensation, reduction, and dehydration reactions, the two carbons of malonyl CoA are added to the growing fatty acyl moiety on FAS.
- FAS are then recharged with another malonyl moiety, and the cycle continues.
- Each turn of the cycle results in the addition of a two-carbon group to the fatty acid moiety as well as the use of one ATP, one acetyl CoA, and two NADPH.
- When the cycle has completed seven turns, the 16-carbon fatty acid (palmitate) is released from FAS.
- Acetyl CoA carboxylase : Transforms acetyl CoA to malonyl CoA with the use of biotin and bicarbonate as cofactors. Requires one ATP.
- Malonyl CoA transferase : Transfers the malonyl CoA molecule to FAS.
- FAS: This collection of enzymes transfers the two carbons of malonyl CoA to the carboxyl end of the growing chain of the fatty acyl moiety. Requires two NADPH.
- Insulin stimulates fatty acid synthesis by dephosphorylating and, therefore, activating acetyl CoA carboxylase.
- Glucagon and epinephrine inhibit fatty acid synthesis by inactivation of acetyl CoA carboxylase.
- Fatty acid synthesis is a critical anabolic pathway in most organisms.
- In addition to being the major component of membranes, fatty acids are important energy storage molecules, and fatty acyl derivatives possess a variety of physiological functions, including post-translational modification of numerous proteins.
- Fatty acid biosynthesis is important for cell growth, differentiation, and homoeostasis.
- David Hames and Nigel Hooper (2005). Biochemistry. Third ed. Taylor & Francis Group: New York.
- Smith, C. M., Marks, A. D., Lieberman, M. A., Marks, D. B., & Marks, D. B. (2005). Marks’ basic medical biochemistry: A clinical approach. Philadelphia: Lippincott Williams & Wilkins.
- John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition. Philadelphia: USA.