Metabolism: Acetyl-CoA and fatty acid synthesis

We generally associate glycolysis with its main function: to convert glucose to pyruvate, which is transported into mitochondria and converted to acetyl-CoA, feeding the citric acid cycle. However, the acetyl-CoA created from pyruvate inside the mitochondria can be also converted to citrate molecules, shuttled back to the cytosol, and reconverted to acetyl-CoA, where it is used to synthesize fatty acids such as palmitate (shown in Figure 1).

Figure 1 Palmitate ($C_{16}{H}_{3}2O_2$‍)

The synthesis of palmitate occurs in the cytosol according to the two-part reaction formula shown in Equations 1 and 2.

The conversion of acetyl-CoA to malonyl-CoA is catalyzed by the enzyme acetyl-CoA carboxylase, whereas the conversion of citrate to acetyl-CoA in the cytosol is catalyzed by the enzyme citrate lyase according to Equation 3.

Both citrate lyase and acetyl-CoA carboxylase are subject to multiple types of enzymatic regulation. For instance, acetyl-CoA carboxylase is activated by citrate. This type of enzymatic regulation is commonly called a feedforward loop.