Kinetic Mechanisms of Cholesterol Synthesis: A Review

Abstract

Increased levels of cholesterol lead to critical health risk factors such as hypercholesterolemia and atherosclerosis in the human system. Regulation of cholesterol synthesis in mammals, especially in humans, is required for a healthy lifestyle. Cholesterol synthesis from acetyl Co-A in liver involves more than 10 enzymes, beginning with acetoacetyl Co-A thiolase, to desmosterol reductase. Among these, 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGR) could be involved in the rate-determining step of cholesterol synthesis. Statins are used to control HMGR. Because statins possess many side effects, an alternate drug for hypercholesterolemia with minimum or no side effects is in great demand. The first and foremost step in drug design is to select a suitable drug target, most likely an enzyme inhibitor. In this regard, an in-depth study of the kinetics of the enzymes involved in cholesterol synthesis is required for a preferred drug target, which, in turn, requires a thorough knowledge of the mechanis...