The biosynthesis of mevalonic acid from 1-C14-acetate by a rat liver enzyme system.

Although it has been conclusively demonstrated in numerous reports that acetate and mevalonic acid are converted to squalene or sterols (3-lo), it has not been proved that mevalonic acid is formed from acetate by a mammalian enzyme system. Evidence has been presented, however, for the formation of this compound from P-hydroxy, P-methyl glutaryl coenzyme A in the presence of reduced triphosphopyridine nucleotide by a cell-free extract of yeast (11-12). In the present work the rat liver enzyme system of Bucher and McGarrahan (3) was fractionated with ammonium sulfate, and the cofactor requirements for the conversion of acetate to sterols by this system were determined. The conversion of l-C% acetate to mevalonic acid by this system was demonstrated through the use of a trapping pool of mevalonic acid and subsequent crystallization of the DBED’ salt to constant specific radioactivity. Confirmatory evidence was obtained through conversion of the acid to hydroxamate and benzhydrylamide derivatives. The hydroxamate derivative was chromatographed, eluted, and the specific radioactivity was determined. The benzhydrylamide derivative was crystallized to constant specific radioactivity. The presence of a second radioactive product formed from 1-Ci4-acetate which is very similar in some chromatographic properties to mevalonic acid is also reported.