The role of glycolysis and the pentose-phosphate pathway in fatty acid synthesis

The role of glycolysis and the pentose-phosphate pathway in fatty acid synthesis FC1D - Glycolysis, Gluconeogenesis, and the Pentose-Phosphate Pathway Content Category 1D: Principles of bioenergetics and fuel molecule metabolism

The glycolytic pathway is usually presented in the context of explaining how cells oxidize glucose to create usable energy in the form of ATP. In this respect, the function of glycolysis is to convert glucose to pyruvate, which is transported into mitochondria and converted to acetyl-CoA, which feeds into the citric acid cycle. However, the acetyl-CoA created from pyruvate inside the mitochondria can be converted to citrate molecules, shuttled back to the cytosol, and reconverted to acetyl-CoA, where they can then be used to synthesize fatty acids such as palmitate.

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

The synthesis of palmitate occurs in the cytosol according to the following two-part reaction formula.

7 acetyl-CoA + 7 $C{O}_2$‍ + 7 ATP → 7 malonyl-CoA + 7 ADP + 7 $P_i$‍

Acetyl-CoA + 7 malonyl-CoA + 14 NADPH + $14H^{+}$‍ → palmitate + 7 $C{O}_2$‍ + 8 CoA + 14 NADP+ + $6H_{2}O$‍

The conversion of acetyl-CoA to malonyl-CoA is catalyzed by the enzyme acetyl-CoA carboxylase. The conversion of citrate to acetyl-CoA in the cytosol is catalyzed by the enzyme citrate lyase according to the following reaction formula.

citrate + ATP + CoA + $H_{2}O$‍ → oxaloacetate + acetyl-CoA + ADP + $P_i$‍

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.