<P> In humans, fatty acids are formed from carbohydrates predominantly in the liver and adipose tissue, as well as in the mammary glands during lactation . The cells of the central nervous system probably also make most of the fatty acids needed for the phospholipids of their extensive membranes from glucose, as blood - born fatty acids cannot cross the blood brain barrier to reach these cells . However, how the essential fatty acids, which mammals cannot synthesize themselves, but are nevertheless important components of cell membranes (and other functions described above) reach them is unknown . </P> <P> The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into fatty acids and cholesterol . This occurs via the conversion of pyruvate into acetyl - CoA in the mitochondrion . However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs . This cannot occur directly . To obtain cytosolic acetyl - CoA, citrate (produced by the condensation of acetyl CoA with oxaloacetate) is removed from the citric acid cycle and carried across the inner mitochondrial membrane into the cytosol . There it is cleaved by ATP citrate lyase into acetyl - CoA and oxaloacetate . The oxaloacetate is returned to mitochondrion as malate (and then converted back into oxaloacetate to transfer more acetyl - CoA out of the mitochondrion). The cytosolic acetyl - CoA is carboxylated by acetyl CoA carboxylase into malonyl CoA, the first committed step in the synthesis of fatty acids . </P> <P> Acetyl - CoA is formed into malonyl - CoA by acetyl - CoA carboxylase, at which point malonyl - CoA is destined to feed into the fatty acid synthesis pathway . Acetyl - CoA carboxylase is the point of regulation in saturated straight - chain fatty acid synthesis, and is subject to both phosphorylation and allosteric regulation . Regulation by phosphorylation occurs mostly in mammals, while allosteric regulation occurs in most organisms . Allosteric control occurs as feedback inhibition by palmitoyl - CoA and activation by citrate . When there are high levels of palmitoyl - CoA, the final product of saturated fatty acid synthesis, it allosterically inactivates acetyl - CoA carboxylase to prevent a build - up of fatty acids in cells . Citrate acts to activate acetyl - CoA carboxylase under high levels, because high levels indicate that there is enough acetyl - CoA to feed into the Krebs cycle and produce energy . </P> <P> High plasma levels of insulin in the blood plasma (e.g. after meals) cause the dephosphorylation of acetyl - CoA carboxylase, thus promoting the formation of malonyl - CoA from acetyl - CoA, and consequently the conversion of carbohydrates into fatty acids, while epinephrine and glucagon (released into the blood during starvation and exercise) cause the phosphorylation of this enzyme, inhibiting lipogenesis in favor of fatty acid oxidation via beta - oxidation . </P>

Where do fatty acids enter the krebs cycle