Cholesterol is both an essential component of cell membranes,and it is required for the synthesis of bile acids,steroid hormones,and other important compounds.The human body obtains the needed cholesterol either by intracellular synthesis or by uptake with the diet.An obligatory step in the intracellular synthesis of cholesterol is the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) into mevalonate and CoA by the enzyme HMG-CoA reductase; two molecules of NADPH deliver the four electrons required for this reaction.Human HMG-CoA reductase is a polypeptide chain of 888 amino acids; it includes a membrane-spanning portion (a.a.1-350) and a catalytic portion (a.a.460-888),connected by a long linker polypeptide..The catalytic portion forms a stable tetramer that consists of two dimers,each of which forms two active sites.