Mescaline-induced changes of brain-cortex ribosomes mescaline demethylase activity of brain-cortex soluble supernatant

Slices of brain cortex remove methyl groups from mescaline, but at about one third the rate of a reference compound. The enzyme responsible, a demethylase, is found mostly in the soluble part of the cell and was purified 47-fold. It works best at pH 7.2 to 8.0, is stable for a few days with certain protective chemicals, and is inhibited by p-chloromercuribenzoate. The enzyme converts mescaline into two identified compounds—3,4-dimethoxy-5-hydroxyphenethylamine and 3,5-dimethoxy-4-hydroxyphenethylamine—plus some unidentified derivatives.

Study at a glance

Abstract

Brain-cortex slices demethylate mescaline and p-methoxyacetanilide, a reference O-demethylating substrate, though the rate of demethylation of mescaline is about one third that of the reference substrate. The demethylase activity is localized mostly in the soluble supernatant (105 000 x g). It is purified 47-fold with respect to the demethylation of mescaline by ammonium sulfate precipitation and DEAE cellulose chromatography. The partially purified demethylase, which is stable for 3-5 days at -5 degrees C in the presence of dithiothreitol and glutathione and is inhibited by p-chloromercuribenzoate, has maximal activity at pH between 7.2 and 8.0. It demethylates mescaline into 3,4-dimethoxy-5-hydroxyphenethylamine and 3,5-dimethoxy-4-hydroxyphenethylamine and some unidentified derivatives.