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9.5: Fatty Acid Synthesis

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    When the intake of nutrients exceeds the energy requirements of the body, the acetyl-CoA produced by the degradation of food can be converted into fatty acids and stored as fats. This anabolic process is accomplished using a different set of enzymes than the catabolism of fatty acids discussed earlier. Another difference between the catabolic and anabolic reactions for fatty acids is the location: whereas we saw that catabolism occurs largely in the mitochondria, fatty acid synthesis is run from a single large enzymatic complex in the cytoplasm.

    We will illustrate here the formation of palmitic acid. Fatty acid synthesis (Figure \(\PageIndex{11}\)) starts with the formation of malonyl-CoA. Malonyl-CoA is a 3-carbon molecule also formed from acetyl-CoA and bicarbonate by an enzyme called Acetyl-CoA carboxylase:

    acetyl-CoA + HCO3- + ATP ---> malonyl-CoA + ADP + Pi 

    The acetyl-CoA in the cytoplasm is primarily derived from the mitochondrial acetyl-CoA. Because the inner mitochondrial membrane is impermeable to acetyl-CoA, this compound is exported to the cytoplasm via a citrate-malate shuttle that couples deacetylation in the mitochondrion with acetylation in the cytosol.

    Fatty acid synthesis is carried out  by the fatty acid synthase system, comprised of seven enzymes linked together with an acyl carrier protein (ACP). As mentioned, this complex is found in the cytoplasm. 

    The acetyl-CoA and malonyl-CoA are linked to the synthase and ACP, then there is a sequence of acetyl group transfers that runs a total of seven times to form palmitoyl-ACP, from which the palmitic acid is finally released. Palmitic acid is the precursor for variety of long-chain fatty acids such as stearic acid, palmitoleic acid, and oleic acid. Generally, there is either an elongation or sometimes a desaturation step. 

    Screen Shot 2018-12-23 at 7.28.40 PM.png
    Figure \(\PageIndex{11}\). Fatty acid synthesis

    The overall reaction for the synthesis of palmitic acid from acetyl CoA is as follows:

    8 Acetyl CoA (2C)  + 14 NADPH + 13H+ + 7 ATP→ Palmitate (16C) + 8 CoA-SH + 6 H2O + 14 NADP+ + 7 ADP + 7 Pi

    Each of the fatty acyl chain additions generates an ester bond, which requires a significant energy input: that energy comes from a linked ATP hydrolysis reaction for each chain addition.  These fatty acids are then used to form the triacylglycerol and stored in adipose tissue, which contains the bulk of the energy storage molecules in most animals. Triacylglycerols are synthesized by the reaction of fatty acyl-CoA chains with glycerol-3-phosphate. Two rounds of this reaction yields diacylglygerol-3-phosphate (phosphatidic acid). After the action of phosphatidate phosphatase, the phosphatidic acid is converted to 1,2-diacylglycerol. This reacts with fatty acyl-CoA to form the final triacyglycerol.

    Humans can convert glucose into fatty acids, but we cannot convert fatty acids into glucose because we lack the enzyme necessary to transform acetyl CoA into pyruvate, the compound used in gluconeogenesis. Some plants and bacteria do have the enzyme necessary for this metabolic transformation, so they are capable of producing glucose from fats. 


    9.5: Fatty Acid Synthesis is shared under a CC BY-NC-SA license and was authored, remixed, and/or curated by E. V. Wong.