Metabolism of mevalonic acid in cell-free homogenates of bovine retinas. Formation of novel isoprenoid acids.

The metabolism of 3RS-[2RS-3H]mevalonate in the 10,000 x g supernatant fractions of homogenates of bovine retinas has been studied. Very efficient incorporation of the labeled mevalonate, approaching quantitative utilization of its 3R-isomer, into lipid products was observed. The extent of incorporation into saponifiable lipids was very substantial. Analysis of the labeled saponifiable lipids indicated that these lipids were composed almost exclusively of C15 and C20 isoprenoid acids. The major C15 acids corresponded chromatographically to trans,trans-farnesoic acid and cis,cis-farnesoic acid. The major C20 isoprenoid acids corresponded chromatographically to trans,trans,-trans-geranylgeranoic acid and an unidentified C20 isoprenoid acid containing at least one cis-double bond. Analyses of the nonsaponifiable lipids indicated the presence of labeled squalene, a C30 fraction containing lanosterol and/or 24,25-dihydrolanosterol, and a C27 fraction containing cholesterol, 5 alpha-cholest-7-en-3 beta-ol, 5 alpha-cholesta-8,24-dien-3 beta-ol, 5 alpha-cholesta-7,24-dien-3 beta-ol, and cholesta-5,24-dien-3 beta-ol. Trace components corresponding chromatographically to 5 alpha-cholest-8(14)-en-3 beta-ol and cholesta-5,7-dien-3 beta-ol were also detected.