Hepatic cholesterol synthesis pathway

The hepatic cholesterol synthesis pathway, primarily known as the mevalonate pathway, is a complex series of enzymatic reactions in the liver that converts acetyl-CoA into cholesterol. This pathway is essential for producing cholesterol, which serves as a structural component of cell membranes and a precursor for bile acids, steroid hormones, and Vitamin D. The rate-limiting step is catalyzed by the enzyme HMG-CoA reductase, which reduces HMG-CoA to mevalonate. Dysregulation of this pathway leads to elevated circulating cholesterol levels, a major risk factor for atherosclerosis and coronary heart disease. Pharmacological intervention, most notably through statins, targets this pathway to lower LDL cholesterol and reduce cardiovascular morbidity and mortality. While highly effective, targeting this pathway requires monitoring for side effects such as muscle toxicity and hepatic enzyme elevations.

Other names

Mevalonate pathwayHMG-CoA reductase pathwayCholesterol biosynthetic pathwayIsoprenoid pathway

Competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the pathway, or inhibition of upstream enzymes like ATP citrate lyase to reduce the pool of acetyl-CoA available for cholesterol synthesis.