HMG-CoA Reductase - Importance

Importance

HMG-CoA reductase is a polytopic, transmembrane protein that catalyzes a key step in the mevalonate pathway (MetaCyc mevalonate pathway), which is involved in the synthesis of sterols, isoprenoids and other lipids. In humans, HMG-CoA reductase is the rate-limiting step in cholesterol synthesis and represents the sole major drug target for contemporary cholesterol-lowering drugs.

The medical significance of HMG-CoA reductase has continued to expand beyond its direct role in cholesterol synthesis following the discovery that it can offer cardiovascular health benefits independent of cholesterol reduction. Statins have been shown to have anti-inflammatory properties, most likely as a result of their ability to limit production of key downstream isoprenoids that are required for portions of the inflammatory response. It can be noted that blocking of isoprenoid synthesis by statins has shown promise in treating a mouse model of multiple sclerosis, an inflammatory autoimmune disease.

HMG-CoA reductase is also an important developmental enzyme. Inhibition of its activity and the concomitant lack of isoprenoids that yields can lead to morphological defects.