Vol. ? 2, No. 1, 1963 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS THE FORMATION OF WNYL-ENZYME AND ITS CONVERSION TO FATTY ACIDS AND 8-HYDROXY. @-METHYL GLUTARYL COENZYME A* Jonathan D. Brodie, Gertrude W. Wasson and John W. Porter The Radioisotope Unit, Veterans Administration Hospital and the Department of Physiological Chemistry, University of Wisconsin, Madison, Wisconsin Received May 16, 1963 Previous reports from this laboratory (Brodie, Wasson and Porter, 1962; Brodie, Wasson and Porter, 1963) demonstrated that donyl CoA is a sub- strate for the biosynthesis of mevslonic and long chain fatty acids by a parti- ally purified avian liver enzyme system. These studies also showed that neither acetoacetyl COA nor p-hydroxy, p-methyl glutaryl coenzyme A (HMG- CoA) are intermediates in the formation of mevalonic acid. As a result of these findings it was concluded that acetoacetyl-enzyme and HMG-enzyme are intermediates in the formation of mevalonic acid and that acetoacetyl- enzyme is an intermediate in the formation of fatty acids. Further support for this conclusion is found in the present communication in which evidence is presented for the formation of malonyl-enzyme and for its conversion to HMGCoA and long chain fatty acids. The importance of HMGCoA in the pre- sent studies is found in the fact that this compound is formed, in the absence of TPNH, from the true intermediate in mevalonic acid biosynthesis. Its * This investigation was supported by research grants A-1383 from the National Institute of Arthritis and Metabolic Diseases of the National Institutes of Health, U.S. Public Health Service and 61 G 7 from the American Heart Association. The authors express their appreciation to Mr. E.A. Steberl for the enzyme preparations used in these studies.