Fatty acid biosynthesis is regulated largely by hormonal mechanisms (Figure 18.34). Acetyl-CoA carboxylase, the first enzyme in the pathway, is an important regulatory enzyme for the entire pathway. Fatty acid biosynthesis is inactivated in two ways through control of acetyl-CoA carboxylase activity:

1. Phosphorylation of acetyl-CoA carboxylase by the cAMP-dependent protein kinase (see Figure 13.18) tends to inactivate acetyl-CoA carboxylase by favoring depolymerization to the monomeric form.

2. Long chain fatty acyl-CoAs inactivate acetyl-CoA carboxylase.

Conversely, fatty actid biosynthesis can be activated by insulin as follows (Figure 18.34):

1. Insulin promotes entry of glucose into cells which, in turn, favors production of NADPH via entry of glucose-6-phosphate into the pentose phosphate pathway.

2. Insulin activates the pyruvate dehydrogenase complex, which promotes production of acetyl-CoA .

3. Insulin reverses the effects of the kinase cascade, and stimulates dephosphorylation of acetyl-CoA carboxylase. This, in turn, promotes the conversion of the enzyme to its active, polymeric form.

In addition to hormonal/covalent regulation of acetyl-CoA carboxylase, allosteric interactions of the enzyme with citrate or acyl-CoAs favor polymerization or depolymerization, respectively, of the enzyme.