BIOSYNTHESIS OF LECITHIN IN. BRAIN AND DEGENERATING NERVE. PARTICIPATION OF CYTIDINE DIPHOSPHATE CHOLINE

Abstract

The radioactivity of cytidine diphosphate choline labelled with P32 (CMP-p32ch) was incorporated in vitro into the phosphatides of both hypotonic homogenates of rat brain and mitochondria prepared from isotonic sucrose homogenates. With both preparations the incorporation was increased by addition of D-[alpha], [beta]-diglycerides prepared enzymatically from naturally-occurring lecithins. Hydrolysis of the labelled phosphatides, followed by separation of the hydrolysis products by two-dimensional paper chromatography, indicated that most of the radioactivity was in lecithin (phosphatidyl choline). Only traces of activity were present in phosphatidyl ethanolamine and phosphatidyl serine. There was also some radioactivity in an alkali-stable fraction that was designated "sphingomyelin". These findings are consistent with the view that the phosphatides of brain are formed in situ from smaller molecules and that the metabolic pathways for their formation are similar to those postulated by Kennedy and colleagues for the biosynthesis of phosphatides in chicken liver. The radioactivity of CMP-p32ch also was incorporated into the phosphatides of homogenates of rat sciatic nerve. This incorporation was greater in homogenates prepared from nerves removed 13 days after previous section. It is suggested that these and other increases found in the in vitro labelling of phosphatides in nerves degenerating after previous section, reported elsewhere, represent an increase in the potentiality of the nerve for remyelination. These increases are associated with the increase in the number of Schwann cells in the nerve.