Synthesis and turnover of cerebroside sulfate of myelin in adult and developing rat brain.

The turnover of cerebroside sulfate (sulfatide) was followed in both microsomal and myelin fractions of developing and adult rat brains after an intracerebral injection of Na(2)(35)SO(4). In the adult rats, the specific radioactivity of sulfatide of the microsomal fraction reached a maximum 12 hr after the injection, and after 3 days it was reduced to less than 30% of the maximum. In contrast, the specific radioactivity of the myelin sulfatide did not reach a peak until 3 days after the injection and remained essentially at the same level for as long as 6 months. In the case of 17-day-old rats, the specific radioactivity of myelin sulfatide reached a maximum level around 12 hr after the injection and then appeared to decline. The decline was most marked 2-6 days after the injection, suggesting an apparently rapid turnover of myelin sulfatide. When a correction was made for deposition of newly formed sulfatide, the results indicated that the turnover of myelin in the developing animals was also relatively slow. In vitro experiments with purified myelin and 3'-phosphoadenosine-5'-[(35)S]phosphosulfate showed that myelin does not catalyze the galactocerebroside sulfotransferase reaction. This enzyme was found mainly in the microsomal fraction. In vivo studies suggested that a transfer of sulfatide molecules from the endoplasmic reticulum to myelin might occur. In order to obtain direct evidence for such a transfer, rat brain slices after pulse labeling with Na(2)(35)SO(4) were washed free of the isotope and reincubated with nonlabeled Na(2)SO(4). The specific radioactivity of the microsomal sulfatide declined, with a concomitant rise in the specific radioactivity of the myelin sulfatide. These observations are therefore consistent with the postulate that myelin sulfatide is probably synthesized in the endoplasmic reticulum.