Pyrrolidone carboxylic acid (PCA) is one of the main components (accounting for approximately 12%) of natural moisturizing factors (NMF) in the mammalian epidermal stratum corneum, and it is produced by the degradation of filaggrin. It exhibits multiple biological activities such as skin moisturization, central GABA release, anxiolysis, and auxiliary ethanol metabolism. The content of Pyrrolidone carboxylic acid correlates with the clinical severity of atopic dermatitis lesions, skin barrier function, and inflammation levels, and shows a negative correlation with the expression of TNF-α and IL-13. Pyrrolidone carboxylic acid can serve as a key skin biomarker for skin barrier function and health [1] [2] [3].
In Vivo, Pyrrolidone carboxylic acid releases GABA from the cerebral cortex of freely-moving guinea pigs[1]. Pyrrolidone carboxylic acid displays anti-anxiety effects in rats tested in a simple approach-avoidance conflict situation[1]. Pyrrolidone carboxylic acid forms slowly from intradermally injected [3H]glutamine in male guinea pig epidermis, reaching ~40-45% of total epidermal radioactivity by day 9, with synthesis linked to protein degradation and nonenzymic cyclization of released glutamine as the predominant pathway[3].
In Vitro, Pyrrolidone carboxylic acid in the epidermis is mainly generated via non-enzymatic cyclization of glutamine released from the degradation of structural proteins in the stratum corneum, rather than via direct enzymatic synthesis in the viable epidermal layers[3].
References:
[1]. Pellegrini-Giampietro DE, Moroni F, Pistelli A, et al.. Pyrrolidone carboxylic acid in acute and chronic alcoholism. Preclinical and clinical studies. Recenti progressi in medicina. 1989 Mar;80(3):160-4.
[2]. Jung M, Choi J, Lee SA, et al.. Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis. Journal of dermatological science. 2014 Dec;76(3):231-9.
[3]. Barrett JG, Scott IR. Pyrrolidone carboxylic acid synthesis in guinea pig epidermis. The Journal of investigative dermatology. 1983 Aug;81(2):122-4.
In Vivo, Pyrrolidone carboxylic acid releases GABA from the cerebral cortex of freely-moving guinea pigs[1]. Pyrrolidone carboxylic acid displays anti-anxiety effects in rats tested in a simple approach-avoidance conflict situation[1]. Pyrrolidone carboxylic acid forms slowly from intradermally injected [3H]glutamine in male guinea pig epidermis, reaching ~40-45% of total epidermal radioactivity by day 9, with synthesis linked to protein degradation and nonenzymic cyclization of released glutamine as the predominant pathway[3].
In Vitro, Pyrrolidone carboxylic acid in the epidermis is mainly generated via non-enzymatic cyclization of glutamine released from the degradation of structural proteins in the stratum corneum, rather than via direct enzymatic synthesis in the viable epidermal layers[3].
References:
[1]. Pellegrini-Giampietro DE, Moroni F, Pistelli A, et al.. Pyrrolidone carboxylic acid in acute and chronic alcoholism. Preclinical and clinical studies. Recenti progressi in medicina. 1989 Mar;80(3):160-4.
[2]. Jung M, Choi J, Lee SA, et al.. Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis. Journal of dermatological science. 2014 Dec;76(3):231-9.
[3]. Barrett JG, Scott IR. Pyrrolidone carboxylic acid synthesis in guinea pig epidermis. The Journal of investigative dermatology. 1983 Aug;81(2):122-4.