Control of Melanogenesis In the Human Epidermis by the Redox-Status of Tetrahydrobiopterins

Abstract

Activity of tyrosinase directly controls melanogenesis in the human epidermis. Recently, it has been shown that the biosynthesis and recycling of (6R)L-erythro 5,6,7,8 tetrahydrobiopterin (6-BH4) plays a central role in regulating the supply of L-tyrosine, the substrate for tyrosinase. In this report, we present evidence that 6-BH4 and other tetrahydropterins, have the capacity to regulate tyrosinase activity directly by a specific uncompetitive mechanism. This fine control of tyrosinase activity/melanogenesis in the human epiidermis depends on the redox equilibrium 6-BH4 ↔ dihydropterin ↔ 6-biopterin. The accumulation of 6-biopterin is cytotoxic to normal human melanocytes.