Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Lipid Biosynthesis
Regulation of Fatty Acid Biosynthesis

The rate of FATTY ACID Biosynthesis is determined primarily by the velocity of the acetyl-CoA carboxylase reaction, which yields malonyl-CoA. Acetyl-CoA carboxylase is an allosteric enzyme that exhibits very low activity in the absence of citrate, which acts as an activating modulator. An increase in the concentration of mitochondrial citrate prompts its transport into the Cytosol via shuttle mechanisms. The appearance of citrate in the cytosol serves as an allosteric signal indicating that The Citric Acid Cycle is overloaded with fuel and that excess acetyl-CoA should be stored as fat. By binding to the allosteric site of acetyl-CoA carboxylase, citrate significantly accelerates The conversion of acetyl-CoA into malonyl-CoA. In the cytosol, citrate also serves as a source of acetyl-CoA required for fatty acid synthesis. When palmitoyl-CoA (the product of fatty acid synthesis and the direct precursor of triacylglycerols) is produced in excess, it Functions as an allosteric inhibitor of acetyl-CoA carboxylase. Because Fatty acids are stored not in their free form but as triacylglycerols, the concentration of glycerol phosphate (one of the precursors of triacylglycerols) can exert a regulatory effect on fatty acid synthesis. Other factors, discussed below, coordinate fatty acid biosynthesis with Carbohydrate METABOLISM.

Let us now examine how triacylglycerols are synthesized from Fatty Acids and glycerol.