What is the consequence of having a mutant form of ACC2 that is always active?

• A. Increased fatty acid oxidation
• B. Decreased triglyceride levels
• C. Increased glucose production
• D. Decreased insulin resistance

Answer: (A)

The consequence of having a mutant form of ACC2 (acetyl-CoA carboxylase 2) that is always active relates to its role in fatty acid metabolism. ACC2 is a key enzyme in the de novo lipogenesis pathway, which converts acetyl-CoA to malonyl-CoA—a crucial step in fatty acid synthesis. When ACC2 is constitutively active, there is a continuous production of malonyl-CoA.

Malonyl-CoA plays an essential role in regulating fatty acid metabolism. Specifically, it inhibits carnitine palmitoyltransferase I (CPT1), the enzyme responsible for transporting fatty acids into the mitochondria for oxidation. With a consistently active ACC2 and high levels of malonyl-CoA, this inhibition of CPT1 leads to decreased fatty acid oxidation, as fatty acids are not effectively transported into the mitochondria.

Furthermore, the persistent activation of ACC2 and the resultant accumulation of malonyl-CoA contribute to enhanced fatty acid synthesis rather than oxidation. This can lead to a buildup of fatty acids and triglycerides, as more fatty acids are produced while their breakdown is limited.

Thus, the consequence of having a mutant form of ACC2 that is always active results in