Enzymic conversion of farnesyl pyrophosphate to squalene

Abstract

Squalene synthetase of pig liver has been solubilized and partially purified. This enzyme has a pH optimum of 7.4 and a K m value of 5 × 10 −7 M for farnesyl pyrophosphate. A divalent metal ion, Mg ++ or Mn ++, and NADPH are required for the conversion of farnesyl pyrophosphate to squalene. Inhibition of the reaction is effected in the presence of nerolidyl pyrophosphate and SH inhibitors. Inhibition is also effected by farnesyl pyrophosphate at concentrations greater than 1.0 × 10 −4 M. Farnesyl pyrophosphate reacts with the enzyme to form an enzyme bound intermediate (C 15) with the release of pyrophosphate. A C 30-enzyme compound has also been isolated and this compound has been converted to squalene on addition of NADPH and Mg ++ to the incubation mixture. A mechanism for the conversion of farnesyl pyrophosphate to squalene has been proposed from these findings.