Cholesterol Biosynthesis

Cholesterol biosynthesis is a complex, multi-step metabolic pathway responsible for the endogenous production of cholesterol from simple precursors. This process occurs primarily in the cytosol and endoplasmic reticulum of animal cells, with the liver being a major site. Cholesterol is an essential structural component of cell membranes and serves as a precursor for steroid hormones, bile acids, and vitamin D. The pathway begins with acetyl-CoA as the starting substrate and proceeds through several key intermediates: mevalonate, isoprenoid units (five-carbon chains), squalene (a 30-carbon linear molecule), lanosterol (the first cyclic intermediate), and finally cholesterol. The rate-limiting enzyme is HMG-CoA reductase, which catalyzes conversion of HMG-CoA to mevalonate. Regulation occurs at multiple levels, including transcriptional control by SREBPs and feedback inhibition by cholesterol and its derivatives. Defects or dysregulation in enzymes of this pathway can lead to human diseases. Statins target HMG-CoA reductase to lower blood cholesterol levels therapeutically.

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis.