Metabolism of Functional Groups Modifying the CNS Myelin‐Associated Glycoprotein

Abstract: We have examined the metabolic turnover of the peptide backbone of the CNS myelin‐associated glycoprotein (MAG) and of the fucose and sulfate groups modifying this protein. Rats (20 or 90 days old) were injected intracranially with mixtures of [³H]fucose and [¹⁴C]glycine, [³H]glycine and [³⁵S]sulfuric acid, or [³H]fucose and [³⁵S]sulfuric acid. At times ranging from 30 min to 4 weeks later, myelin was isolated, and radioactivity in MAG was determined following electrophoretic separation. Following the peak of incorporation, glycine‐derived radioactivity in the MAG peptide backbone declined several‐fold during the first week and was then metabolically stable (half‐life ≫ 1 month). Declines with time in [³H]fucose‐ and [³⁵S]sulfate‐derived radioactivity in MAG were similar to that of [³H]glycine, an observation indicating that the fucose and sulfate groups modifying MAG are metabolized together with the peptide backbone as a single metabolic entity. These results were confirmed by experiments involving selective immunoprecipitation of MAG. The rates of incorporation of labeled glycine, fucose, and sulfate into MAG all decreased ∼ 12–fold between 20 days of age and adulthood, a finding providing further evidence for concerted turnover of the entire molecule. Because of this concerted turnover, we suggest that functional groups modifying MAG serve some permanent structural role in protein configuration.