What is the rate-limiting enzyme in cholesterol synthesis?

• A. Acetyl-CoA carboxylase
• B. HMG-CoA hydrolase
• C. Squalene synthase
• D. HMG-CoA reductase

Answer: (D)

The rate-limiting step in making cholesterol is the conversion of HMG-CoA to mevalonate, carried out by HMG-CoA reductase. This step sits at a key control point in the pathway, so changing its activity has the biggest impact on the overall flux toward cholesterol. Because cells regulate this enzyme tightly, high cholesterol levels suppress it, while low cholesterol levels relieve suppression and raise its activity. This is also why statin drugs lower cholesterol by inhibiting HMG-CoA reductase.

Acetyl-CoA carboxylase governs fatty acid synthesis, not cholesterol. HMG-CoA hydrolase isn’t a main, recognized step in cholesterol production. Squalene synthase acts downstream of the rate-limiting step, so it doesn’t dictate the pathway’s overall rate under normal regulation.