Studies on the biosynthesis of cholesterol: XIV. the origin of prenoic acids from allyl Pyrophosphates in liver enzyme systems

Abstract

Allyl pyrophosphates (3,3-dimethylallyl, geranyl, and farnesyl pyrophosphate), which are known intermediates in the biosynthesis of squalene from mevalonate, are also metabolized in the liver by an alternative pathway to acids. The first step in the conversion of the allyl pyrophosphates into the acids (dimethylacrylic, geranoic, and farnesoic acids) is their irreversible dephosphorylation into free prenols by a microsomal phosphatase, which has its optimum pH at around 7.0. In a second step the free prenols are irreversibly dehydrogenated to the acids by liver alcohol dehydrogenase and aldehyde dehydrogenase present in a soluble protein fraction of liver homogenates. This dehydrogenation proceeds best at pH 7.5 and is inhibited by sulfhydryl reagents. The prenols are more specific substrates for liver alcohol dehydrogenase than is ethanol, but they cannot act as substrates for yeast alcohol dehydrogenase. The formation of allyl pyrophosphates, of free prenols, and of prenoic acids from mevalonate was also observed in vivo.