BIOSYNTHESIS OF CHOLESTEROL BY BOVINE AORTA AND MECHANISM OF ACTION OF ALPHA-PARA-CHLOROPHENOXYISOBUTYRIC ACID

The nature and requirements for the biosynthesis of nousaponifiable material (NSF) and cholesterol from acetate-2-14C, acetyl-1-14C CoA and mevalonate-2-14C by cell-free systems from bovine aorta were determined. Low radioactivity was incorporated into cholesterol (60 to 320 CPM per mg), determined as the digitonide and by gas chromatography, using mevalonate as the substrate. No conversion of acetate to NSF and cholesterol was observed. However, acetyl-CoA was converted to NSF. Bovine aorta cell-free systems were shown to convert mevalonate to mevalonic acid-5-phosphate and mevalonic acid-5-pyrophosphate. The majority of the radioactivity was incorporated into a compound tentatively identified as a polar isoprenoid. Mevalonate conversion to NSF and cholesterol was inhibited by α-p-chlorophenoxyisobutyrate (CPIB) and related compounds. Mevalonate kinase was inhibited by CPIB. The inhibition of mevalonate incorporation was prevented by increasing the ATP concentration. CPIB inhibited the biosynthesis of fatty acids by homogenates of bovine aorta and the conversion of acetate to carbon dioxide. © 1969.