Metabolism of Phosphate and Sulfate Groups Modifying the P 0 Protein of Peripheral Nervous System Myelin

We have examined the metabolism of phosphate and sulfate groups modifying the P 0 protein, the major protein of peripheral nervous system myelin, using an in vitro incubation system. Incorporation of [ 3 H]leucine into the P 0 peptide backbone decreased ∼25‐fold between 10 and 90 days of age, a finding reflecting a decreased rate of myelin synthesis in the older animals. In contrast, incorporation of [ 32 P]phosphate into P 0 decreased only four‐ to fivefold, a result indicating that phosphate groups are metabolized independently of the peptide backbone. Developmental decreases in the incorporation of sulfate groups into P 0 were similar to those seen for leucine, an observation suggesting that this modifying group is metabolized together with the peptide backbone as a single metabolic entity. The time course of labeling of P 0 isolated from the starting homoge‐nate and from myelin was also compared. Results are consistent with sulfation of P 0 protein taking place before insertion of newly synthesized P 0 into myelin. In contrast, incorporation of phosphate into P 0 appears to involve both the newly synthesized pool and the preexisting pool of P 0 in myelin. Presumably, entry of phosphate into P 0 in myelin involves turnover of preexisting phosphate groups and re‐phosphorylation by myelin protein kinases. Developmental decreases in the specific activity of P 0 phosphate groups in myelin are consistent with the presence of a small, rapidly turning‐over pool of phosphorylated P 0 (perhaps associated with the axon‐myelin interface), which does not increase to the same extent as the marked increase in bulk myelin that occurs during development.