Biosynthesis of Pyrrolidone Carboxylic Acid in Hairless Mouse Epidermis

[3H]Glutamic acid incorporated in vivo into hairless mouse epidermal pyrrolidone carboxylic acid (PCA) was followed with time after a single subcutaneous injection. PCA specific activity increased slowly, reaching a peak at 3 to 4 days after injection of the labeled amino acid, after which it slowly declined. Incorporation of [3H]glutamic acid into epidermal PCA was markedly inhibited by a single topical application of cycloheximide. Topical application of cycloheximide 2hr prior to [3H]glutamate injection caused a significantly greater reduction in PCA specific activity (determined 3 days after injection) than cycloheximide treatment 3hr after administration of the labeled amino acid. Ninety-seven percent of the PCA content of hairless mouse epidermis was shown to reside in the stratum corneum. These observations indicate the involvement of protein synthesis in the formation of PCA from glutamic acid rather than a direct conversion of the amino acid. The high level of PCA in mammalian epidermis appears to be caused by its accumulation in the stratum corneum accompanied by a relatively slow rate of PCA turnover in comparison to other tissues