Figure 2.

Filaggrin and its metabolism. FLG is produced in the SG as profilaggrin (FLG polymer) and is stored in keratohyalin granules. At the transition to the SC, the polymer is processed to the monomer by proteases such as Prss8 and SASPase and then binds to keratin and forms the fundamental structure of the corneocytes. At the outermost layer of the SC, FLG is citrullinated by peptidylarginine deiminase and then dissociated from keratin filaments. These dissociated FLG are degraded to free amino acids, including glutamine, arginine, and histidine. The FLG-derived histidine-rich proteins are converted into urocanic acid (UCA) and pyrrolidine carboxylic acid (PCA) by proteases. Zn facilitates FLG production by increasing the activity of Prss8. Alternatively, Zn can also suppress FLG metabolism by decreasing PAD activity. Moreover, Zn is required for histidine conversion to UCA.