Dolichyl phosphate metabolism in brain. Developmental increase in polyisoprenyl phosphate phosphatase activity.

The enzymatic dephosphorylation of endogenous and exogenous dolichyl phosphate (Dol-P) by membrane preparations from calf brain has been reported previously (Burton, W.A., Scher, M.G., and Waechter, C. J. (1981) Arch. Biochem. Biophys. 208, 409-417). The study presented here shows that polyisoprenyl phosphate phosphatase activity increases with age in crude microsomal fractions from white (glial-enriched) and grey (neuronal-enriched) matter of pig brain. A kinetic analysis of grey matter phosphatase activity revealed that the apparent Km values for Dol-P are similar for membranes from adults (0.13 mM) and prenatal subjects (0.12 mM), but the Vmax is significantly higher in adults. In direct contrast to this result, the specific activity of dolichol kinase is nearly 2-fold higher in membranes from pig brain grey matter of prenatal subjects as compared to identical preparations from animals 90 days of age. While the changes in kinase and phosphatase activity are approximately 2-fold, reciprocal changes in these activities would enhance shifts in the metabolic balance of a phosphorylation-dephosphorylation process. In another aspect of this study on polyisoprenyl phosphate phosphatase in nervous tissue, membrane preparations from calf brain are shown to dephosphorylate S- and R-Dol-P. Similar apparent Km values were obtained for S-Dol-P and R-Dol-P, but the Vmax for the dephosphorylation reaction was found to be 1.8-fold greater for S-Dol-P. These results extend the description of polyisoprenyl phosphate phosphatase activity in brain and provide information on developmental changes in phosphatase and kinase activities involved in Dol-P metabolism in nervous tissue.