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

Location

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

Products:

  • 1 molecule of palmitate (16-carbon fatty acid)
  • 7 H2O

Fatty Acid Synthesis Pathway

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.

Fatty Acids Synthesis

Important enzymes

  • 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.

Activators:

  • Insulin stimulates fatty acid synthesis by dephosphorylating and, therefore, activating acetyl CoA carboxylase.

Inhibitors:

  • Glucagon and epinephrine inhibit fatty acid synthesis by inactivation of acetyl CoA carboxylase.

Significance

  • 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. 

References

  1. David Hames and Nigel Hooper (2005). Biochemistry. Third ed. Taylor & Francis Group: New York.
  2. 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.
  3. John W. Pelley, Edward F. Goljan (2011). Biochemistry. Third edition. Philadelphia: USA.
  4. https://www.sciencedirect.com/topics/medicine-and-dentistry/fatty-acid-synthesis

About Author

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Sagar Aryal

Sagar Aryal is a microbiologist and a scientific blogger. He attended St. Xavier’s College, Maitighar, Kathmandu, Nepal, to complete his Master of Science in Microbiology. He worked as a Lecturer at St. Xavier’s College, Maitighar, Kathmandu, Nepal, from Feb 2015 to June 2019. After teaching microbiology for more than four years, he joined the Central Department of Microbiology, Tribhuvan University, to pursue his Ph.D. in collaboration with Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrucken, Germany. He is interested in research on actinobacteria, myxobacteria, and natural products. He has published more than 15 research articles and book chapters in international journals and well-renowned publishers.

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