How is cholesterol biosynthesis regulated?

Cholesterol synthesis is tightly regulated at multiple levels. HMG-CoA reductase (rate-limiting enzyme converting HMG-CoA to mevalonate) is the primary control point. Regulation includes: transcriptional control by SREBP (sterol regulatory element-binding protein) - low cholesterol activates SREBP, inducing HMG-CoA reductase expression; translational and post-translational control affecting enzyme stability; phosphorylation by AMPK (inactivates enzyme when energy is low); and direct inhibition by cholesterol and oxysterols. Statins competitively inhibit HMG-CoA reductase, lowering cholesterol synthesis. Feedback regulation ensures cells make cholesterol when needed while preventing overaccumulation.