Fatty acid synthesis

Fatty acid synthesis occurs in the cytosol of the living cell using two carbon units (acetyl units) that are the result of glucose oxidation or amino acid degradation. Fatty acid synthesis begins with acetyl CoA. Acetyl CoA is converted to malonyl CoA with the addition of one carbon (from bicarbonate) in the presence of the enzyme acetyl CoA carboxylase. The reaction uses the energy from one molecule of ATP and biotin as a coenzyme. This reaction is the first committed step in the reaction sequence that results in the synthesis of a fatty acid. The activated carbon dioxide attached to the biotin-enzyme complex is transferred to the methyl end of the substrate. Although most fatty acids synthesized in mammalian cells have an even number of carbons, this first committed step yields a three-carbon product. This results in an asymmetric molecule that becomes vulnerable to attack (addition) at carbon 2 with the subsequent loss of the terminal carbon. The vulnerability is conferred by the fact that both the carboxyl group at one end and the CoA group at the other end are both powerful attractants of electrons from the hydrogen of the middle carbon. This leaves the carbon in a very reactive state, and a second acetyl group carried by a carrier protein with the help of phosphopantethine, which has a sulfur group connection, can be joined to it through the action of the enzyme malonyl transferase. Subsequently, the “extra” carbon is released via the P ketoacyl enzyme synthase, leaving a four-carbon chain still connected to an SH group at the carboxyl end. This SH group is the docking end for all the enzymes that comprise the fatty acid synthase complex. These enzymes catalyze the addition of two-carbon acetyl groups in sequence to the methyl end of the carbon chain until the final product, palmityl CoA, and then the 16-carbon palmitic acid is produced. Members of this fatty acid synthase complex include the aforementioned malonyl transferase and p ketoacyl synthase; P ketoacyl reductase, which catalyzes the addition of reducing equivalents carried by FMN; and an acyl transferase.