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 were 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, 5α-cholest-7-en-3β-ol, 5α-cholesta-8,24-dien-3β-ol, 5α-cholesta-7,24-dien-3β-ol, and cholesta-5,24-dien-3β-ol. Trace components corresponding chromatographically to 5α-cholest-8(14)-en-3β-ol and cholesta-5,7-dien-3β-ol were also detected.