Which amino acid substitution would most effectively create a constantly active variant of ACC2?

• A. Threonine
• B. Serine
• C. Tyrosine
• D. Alanine

Answer: (D)

To determine which amino acid substitution would most effectively create a constantly active variant of ACC2, it's essential to consider the structural and functional roles of the amino acids involved in the enzyme's activity.

ACC2 (acetyl-CoA carboxylase 2) is involved in lipid metabolism, and its activity is typically regulated by various mechanisms, including phosphorylation and allosteric modulation. Substituting an amino acid can influence the enzyme's conformation, interaction with other molecules, and overall activity.

Choosing alanine as the substitution is significant because it is a non-polar, hydrophobic amino acid that can facilitate a more stable and possibly less regulated conformation. Its lack of a functional side chain allows for better accommodation in the hydrophobic core of proteins, which might help maintain an active site in a conformation that favors continual activity. This can potentially prevent the binding of regulatory molecules that normally would inhibit the enzyme's activity.

In contrast, other amino acids like threonine, serine, and tyrosine all possess hydroxyl or larger side chains that may introduce steric hindrance or polar interactions that could destabilize a constantly active form. These substitutions might create a scenario where regulatory controls can still bind, which could lead to the enzyme being