Fatty acid synthesis ( Cytosolic acetyl CoA production)

Carbohydrates and proteins obtained from the diet in excess of the body’s needs for these nutrients can be converted to fatty acids. In adults, de novo fatty acid synthesis occurs primarily in the liver and lactating mammary glands and, to a lesser extent, in adipose tissue. This cytosolic process is endergonic  and reductive. It incorporates carbons from acetyl coenzyme A (CoA) into the growing fatty acid chain, using ATP and reduced nicotinamide adenine dinucleotide phosphate (NADPH). [Note: Dietary TAG also supply fatty acids.

The first step in fatty acid synthesis is the transfer of acetate units from mitochondrial acetyl CoA to the cytosol. Mitochondrial acetyl CoA is produced by the oxidation of pyruvate (see p. 109) and by the catabolism of certain amino acids . However, the CoA portion of acetyl CoA cannot cross the inner mitochondrial membrane, and only the acetyl portion enters the cytosol. It does so as part of citrate produced by the condensation of acetyl CoA with oxaloacetate (OAA) by citrate synthase (Fig. 1).
[Note: The transport of citrate to the cytosol occurs when the mitochondrial citrate concentration is high. This is observed when isocitrate dehydrogenase of the tricarboxylic acid (TCA) cycle is inhibited by the presence of large amounts of ATP, causing citrate and isocitrate to accumulate . Therefore, cytosolic citrate may be viewed as a high-energy signal. Because a large amount of ATP is needed for fatty acid
synthesis, the increase in both ATP and citrate enhances this pathway.] In the cytosol, citrate is cleaved to OAA and acetyl CoA by ATP citrate lyase.

Figure 1:  Production of cytosolic acetyl coenzyme A (CoA). [Note: Citrate is transported by the tricarboxylate transporter system.] ADP = adenosine monophosphate; Pi = inorganic phosphate.