NATURAL MOISTURIZING AGENT IN SKIN 359 occurring in the skin is surprisingly high (2% by weight). Speaking only from a teleological viewpoint, it would seem that the production of large amounts of the material almost exclusively in the skin must serve some function. At the pH of skin, it can be shown that PCA exists almost entirdy in the salt form. In this form, it is found to be highly hygroscopic and at higher relative humidities dissolves in its own water of hydration. An- alytical studies have established a relationship between the amount of this material found in the stratum corncure and the moisture-binding ability of the stratum corneum. The pathway by which this material is synthesized in the skin is un- known. The aqueous extracts of the skin are relatively rich in free amino acids. It has been proposed that these arise from the catabolic breakdown of proteins during keratinization. Since PCA can be formed via the cyclization of glutamic acid with heat, it is possible that some enzymatic cyclization of glutamic acid occurs in the skin. It has been shown (26, 27) that in the enzymatic synthesis of gluta- mine from glutamic acid there is formed an intermediate T-activated glutamate. In the presence of NH• q- ions this is converted to gluta- mine. In the absence of NH4 q- ions, however, the intermediate is con- verted into PCA. Attempts were made to determine whether glutamic acid in skin could act as a direct precursor of PCA, perhaps via formation of an 3'- activated glutamate. Rat skin homogenates were used in the experi- ments after the presence of PCA was established in both guinea pig skin and rat skin. Under the conditions used in these experiments, PCA was not formed from glutamic acid. Obviously, this does not preclude the possibility that it could form under different conditions. An alternative pathway by which PCA may be formed may involve the catabolism of proteins occurring during keratinization. If an acti- vated glutamate is formed during protein catabolism, this may be con- verted directly into PCA. Thus, protein-bound glutamate rather than free glutamate may represent the precursor of PCA. Further experi- mentation in this area is needed. (Received September 20, 1966) REFERENCES (1) Blank, I. H., Factors which influence the water content of the stratum corneum, J. Invest. Dermatol, 18, 433 (1952). (2) Idem., Further observations on factors which influence the water content of the stratum corneum, ibid., 21,259 (1953). (3) Kligman, A. 1Vi., The Biology of the Stratum Corneum, in 1Vfontagna, W., and Lobitz, W. C., Jr., The Epidermis, Academic Press, New York, 1964.

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