Cholesterol on the Scene

Abstract

Cholesterol was discovered in 1815 by the French chemist Michel E. Chevreul who found it in human gall stones. Its precise molecular structure, shown in Fig. 2.9a, remained however unknown until 1932. In the following decades the biosynthetic pathway to cholesterol was worked out, and during the 1970s and 1980s the relationship between the molecular evolution of sterols and the evolution of species was unravelled. The actual regulation of the cholesterol biosynthesis in humans by low density lipoprotein receptors became clarified in the last quarter of the 20th century. All this important work led to three Nobel Prizes, the 1927 Chemistry Prize to Heinrich O.Wieland for his work on cholesterol structure, the 1964 Physiology and Medicine Prize to Konrad Bloch for his work on cholesterol synthesis, and the 1985 Physiology and Medicine Prize to Michael S. Brown and Joseph L. Goldstein for their work on regulation of cholesterol biosynthesis. In total fourteen Nobel Prizes have been awarded to sterols or topics related to sterols. Research on cholesterol has undoubtedly been a key issue in the 20th century. If cholesterol has had high priority as a research area, it has drawn an even higher attention among the public. The reason for this is that cholesterol is thought to be related to the number one killer of Western populations: coronary heart disease and atherosclerosis. It is also associated with adiposis which presents an increasing problem globally. Therefore, cholesterol is probably the lipid that has the worst reputation. This is somewhat of a paradox since cholesterol is both an important structure builder in all cells of our body in addition to being an important metabolite and source of important vitamins and hormones. Few realize, that cholesterol is the single most abundant type of molecule in our plasma membranes, accounting for 30–50%of the lipid molecules, and that all eukaryotic organisms on Earth use similar amounts of cholesterol (or related sterols) in their plasma membranes. So cholesterol is an absolutely essential lipid for the higher forms of life.We shall in this chapter advocate the viewpoint that part of cholesterol’s success in life is due to its unique capacity of imparting to lipid membranes some very special physical properties. And we shall learn that Nature has taken great care and been spending a long time evolving this unique molecule.