Which of the following inhibits the activity of acetyl-CoA carboxylase?
High-Yield Explanation
The key thing to remember here is that acetyl-CoA carboxylase catalyzes the first and rate-limiting step of fatty acid synthesis. If you got that far, you could have figured out which of the choices would inhibit the synthesis of fatty acids. Ceainly glucagon, a catabolic hormone released in response to low blood glucose, would be a likely candidate to inhibit the synthesis of fatty acids. In fact, glucagon inhibits fatty acid synthesis by a cAMP-dependent phosphorylation of acetyl-CoA carboxylase. Conversely, glucagon stimulates fatty acid oxidation. Citrate is a key player in fatty acid synthesis (citrate shuttle). Therefore, the presence of citrate would stimulate, not inhibit, acetyl-CoA carboxylase. A high-carbohydrate, low-fat diet (would stimulate, not inhibit, the synthesis of fatty acids. In contrast to glucagon, insulin is an anabolic hormone that promotes fatty acid synthesis and therefore would stimulate acetyl-CoA carboxylase. It does so by dephosphorylating the enzyme. Ref: Botham K.M., Mayes P.A. (2011). Chapter 23. Biosynthesis of Fatty Acids & Eicosanoids. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper's Illustrated Biochemistry, 29e.