Studies on the biosynthesis of cholesterol. 5. Biosynthesis of squalene from dl-3-hydroxy-3-methyl-[2–14C]pentano-5-lactone

Abstract

3-Hydroxy-3-methylpentaneo- 5- lactone (mevalonic lactone) and a number of other C6 compounds related to it were synthesized and labeled with C14 in position 2. In liver homogenates (2-C14) mevalonic acid is an efficient precursor not only of sterols but also of squalene provided that the incubations are made anaerobically. Mitochondria are not required for the biosynthesis of either squalene or sterol. (C14) Squalene biosynthesized from (2-C14)-mevalonic acid was degraded chemically and contained only 6 labeled positions in the chain of the molecule; the branched methyl-carbon atoms of squalene were not labeled. The results indicate that all carbon atoms in mevalonic acid retain their individuality during biosynthesis. Six substances related to mevalonic acid (all being anhydro compounds of the acid) were also tested as possible intermediates in the biosynthesis of squalene and sterol, but all gave negative results.