Meeting Summary Coordinate Regulation of Cholesterol Metabolism

A NATO-sponsored Advanced Research Workshop (ARW 990-83) on "Coordinate Regulation of Cholesterol Metabolism" was held from October 1-3, 1984, in Sante Fe, New Mexico. The Giovanni Lorenzini Foundation of Italy was also a sponsor. The organizing director was Dr. Ajit Sanghvi, University of Pittsburgh; the co-directors were Drs. Giovanni Galli, University of Milan, Italy, and Terence J. Scallen, University of New Mexico. Drs. David Kritchevsky, The Wistar Institute, Philadelphia, and George Vahouny, George Washington University, Washington, D.C., served on the advisory committee. The last 10 years have provided considerable information on the regulation of cholesterol metabolism via lipoprotein receptor action in various types of cells. A significant body of information about in vitro changes in the activities of cholesterol-metabolizing enzymes has also developed. Changes in the state of phosphorylation of HMG-CoA reductase by experimental manipulations has been shown to be correlated with changes in the enzyme activity. The experimental systems used in these studies have used broken-cell preparation, intact heptatocytes, and whole animals. Similar but less extensive information has recently been gathered for acyl-coA:cholesterol acytransferase (ACAT) and cholesterol 7a-hydroxylase, the other two major enzymes responsible for cholesterol metabolism in the liver cell. There is debate as to whether phosphorylation/dephosphorylation of these enzymes plays a role in vivo and, if it does, the extent of its significance. However, those who suggest enzyme phosphorylation/dephosphorylation as a possible in vivo mechanism for regulating cholesterol flow within the cell suggest it as only a short-term regulatory phenomenon; changes in protein synthesis are required for the long-term.