Category: biosynthesis
De novo cholesterol biosynthesis — ~30 enzymatic steps from acetyl-CoA via the mevalonate pathway. HMG-CoA reductase (HMGCR) is rate-limiting and is the statin target. Diurnal regulation peaks at night, which is why short-half-life statins (simvastatin, fluvastatin) are dosed at bedtime. Sterol-regulatory binding (SREBP-2) downregulates HMGCR when intracellular cholesterol rises — the homeostatic loop statins exploit (cells respond to drug-lowered cholesterol by upregulating LDL-R, which is the actual therapeutic mechanism).