Cholesterol in the year 2000

Cholesterol research was one of the key areas of scientific investigation i n the 20th century. Little was known about the structure of cholesterol unt il the pioneering research of A. Windaus and H. Wieland in the first part o f the century. The structure of cholesterol was completely elucidated in 19 32. With the development of isotopic tracers in the 1930s studies on choles terol biosynthesis were initiated. In 1942 K. Bloch and D. Rittenberg showe d that deuterium-labeled acetate was incorporated into the ring structure a nd side chain of cholesterol. Another important discovery from Bloch's labo ratory was that squalene was a precursor of cholesterol. In 1956, the main elements of the biosynthetic pathway became known when isopentenyl pyrophos phate was discovered as a precursor. In 1966, J. Cornforth and G. Popjak pr edicted that there were 16 234 possible stereochemical pathways by which me valonate could be converted into squalene. They subsequently showed which o f these pathways was correct. In the 1970s and 1980s K. Bloch was able to p rovide intriguing evidence for an evolutionary advantage of cholesterol ove r lanosterol or some of the intermediates in the conversion of lanosterol t o cholesterol. The last quarter of the 20th century was when M. Brown and J . Goldstein showed that the low density lipoprotein receptor was a key regu lator of cholesterol homeostasis. They have also demonstrated that choleste rol balance in the cell is transcriptionally regulated via the sterol regul atory element binding protein. In the later part of the 20th century drugs were developed that effectively lower plasma cholesterol and lessen the ris k of atherosclerosis and cardiovascular disease. (C) 2000 Elsevier Science B.V. All rights reserved.