Question

Pharmacological inhibition of acetyl-CoA carboxylase has been proposed as a treatment for obesity. Explain why this enzyme would appear to be a good anti-obesity drug target.

Short answer

Lowering malonyl-CoA levels, which is the product of acetyl-CoA carboxylase reaction, would boost fatty acid oxidation, and, as a result, the fat accumulation (triacylglycerols) would be reduced.

Step-by-step solution

Step 1: Acetyl-CoA carboxylase enzyme

Acetyl-CoA carboxylase catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA. It is the first step in the fatty acid synthesis.

Step 2: Acetyl-CoA carboxylase enzyme would appear to be a good anti-obesity drug target

One of the potential treatments for obesity is the suppression of acetyl-CoA carboxylase. This enzyme is regarded as one of the most promising anti-obesity therapeutic targets.

Malonyl-CoA is an intermediary substrate involved in fatty acid metabolism regulation produced by the action of acetyl-CoA carboxylase.

The number of fatty acids available for storage as triacylglycerols could be reduced if this pathway is blocked. The malonyl-CoA produced prevents the transport of fatty acyl-CoA to mitochondria.

Conclusion

Lowering malonyl-CoA levels would decrease fatty acid synthesis and promote fatty acid oxidation. It will reduce the amount of fatty acid and hence minimize fat storage (triacylglycerols).