D-tyrosine negatively regulates melanin synthesis by competitively inhibiting tyrosinase activity

Pigment Cell Melanoma Res. 2018 May;31(3):374-383. doi: 10.1111/pcmr.12668. Epub 2017 Nov 27.

Abstract

Although L-tyrosine is well known for its melanogenic effect, the contribution of D-tyrosine to melanin synthesis was previously unexplored. Here, we reveal that, unlike L-tyrosine, D-tyrosine dose-dependently reduced the melanin contents of human MNT-1 melanoma cells and primary human melanocytes. In addition, 500 μM of D-tyrosine completely inhibited 10 μM L-tyrosine-induced melanogenesis, and both in vitro assays and L-DOPA staining MNT-1 cells showed that tyrosinase activity is reduced by D-tyrosine treatment. Thus, D-tyrosine appears to inhibit L-tyrosine-mediated melanogenesis by competitively inhibiting tyrosinase activity. Furthermore, we found that D-tyrosine inhibited melanogenesis induced by α-MSH treatment or UV irradiation, which are the most common environmental factors responsible for melanin synthesis. Finally, we confirmed that D-tyrosine reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Taken together, these data suggest that D-tyrosine negatively regulates melanin synthesis by inhibiting tyrosinase activity in melanocyte-derived cells.

Keywords: D-tyrosine; L-tyrosine; melanin; melanogenesis; tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Melanins / biosynthesis*
  • Melanocytes / metabolism*
  • Melanocytes / pathology
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / metabolism*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism*
  • Tyrosine / pharmacology*
  • Ultraviolet Rays

Substances

  • Melanins
  • Neoplasm Proteins
  • Tyrosine
  • Monophenol Monooxygenase