Study of tyrosine and dopa enantiomers as tyrosinase substrates initiating l- and d-melanogenesis pathways

Biotechnol Appl Biochem. 2021 Aug;68(4):823-831. doi: 10.1002/bab.1998. Epub 2020 Aug 18.

Abstract

Tyrosinase starts melanogenesis and determines its course, catalyzing the oxidation by molecular oxygen of tyrosine to dopa, and that of dopa to dopaquinone. Then, nonenzymatic coupling reactions lead to dopachrome, which evolves toward melanin. Recently, it has been reported that d-tyrosine acts as tyrosinase inhibitor and depigmenting agent. The action of tyrosinase on the enantiomers of tyrosine (l-tyrosine and d-tyrosine) and dopa (l-dopa and d-dopa) was studied for the first time focusing on quantitative transient phase kinetics. Post-steady-state transient phase studies revealed that l-dopachrome is formed more rapidly than d-dopachrome. This is due to the lower values of Michaelis constants for l-enantiomers than for d-enantiomers, although the maximum rates are equal for both enantiomers. A deeper analysis of the inter-steady-state transient phase of monophenols demonstrated that the enantiomer d-tyrosine causes a longer lag period and a lower steady-state rate, than l-tyrosine at the same concentration. Therefore, d-melanogenesis from d-tyrosine occurs more slowly than does l-melanogenesis from l-tyrosine, which suggests the apparent inhibition of melanin biosynthesis by d-tyrosine. As conclusion, d-tyrosine acts as a real substrate of tyrosinase, with low catalytic efficiency and, therefore, delays the formation of d-melanin.

Keywords: dopa; lag phase; melanogenesis; tyrosinase; tyrosine.

MeSH terms

  • Catalysis
  • Dihydroxyphenylalanine / chemistry*
  • Fungal Proteins / chemistry*
  • Kinetics
  • Melanins / chemical synthesis*
  • Melanins / chemistry
  • Monophenol Monooxygenase / chemistry*
  • Oxidation-Reduction
  • Stereoisomerism
  • Tyrosine / chemistry*

Substances

  • Fungal Proteins
  • Melanins
  • Tyrosine
  • Dihydroxyphenylalanine
  • Monophenol Monooxygenase