Functions of cholesterol

Sterols are important constituents of the cell membranes of most eukaryotic cells. The cell membranes of terrestrial vertebrates, including man, contain a single major sterol species—cholesterol. Cholesterol is found particularly in external cellular membranes (plasma membranes) and in the layers that make up the myelin sheaths in the central and peripheral nervous systems. In plasma membranes, the cholesterol molecules are intercalated between the phospholipid molecules of each monolayer and reduce the movement of their acyl chains (reduced “membrane fluidity”). Sterols also exert a direct effect on proteins in the membrane. For example, the function of the human red cell hexose transporter is profoundly affected by the content of cholesterol in the membrane and this cannot be related to changes in fluidity.1 It has been discovered recently that cholesterol has important interactions with proteins which control embryonic development—the hedgehog proteins.2 During biosynthesis, these proteins catalyse their own cleavage and the subsequent attachment of cholesterol to the amino terminal domain. This has a profound effect on the range of action of these signalling molecules.3 4 In the mouse, the absence of a functional gene for one of the hedgehog proteins (sonic hedgehog) results in multiple malformations including holoprosencephaly.2Holoprosencephaly in mice can also be caused by giving them an inhibitor of cholesterol synthesis, AY9944. In addition to its functions in cell membranes and in development, cholesterol acts as the precursor for the steroid hormones and bile acids. The bile acids, in turn, are necessary for efficient absorption of dietary lipids, including cholesterol and the fat soluble vitamins.

Given these functions of cholesterol, it is not surprising that disorders of cholesterol biosynthesis can lead to syndromes featuring major malformations, low maternal oestriol concentrations, failure of development of male external genitalia due to testosterone deficiency, and mental retardation associated with …