Study of tyrosine and dopa enantiomers as tyrosinase substrates initiatingl‐ andd‐melanogenesis pathways

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.

Hop Flower Supercritical Carbon Dioxide Extracts Coupled with Carriers with Solubilizing Properties—Antioxidant Activity and Neuroprotective Potential

“…Last but not least, inhibition of tyrosinase, which is not considered a direct target for the prevention of neurodegeneration, might be helpful in neuroprotection. This enzyme converts tyrosine to L-DOPA and then to dopaquinone [ 41 ]. By inhibiting the activity of tyrosinase, the degradation of L-DOPA is reduced, resulting in higher levels of dopamine precursors.…”

Considerations about the Continuous Assay Methods, Spectrophotometric and Spectrofluorometric, of the Monophenolase Activity of Tyrosinase

“…Indeed, if the initial velocity values are adjusted, with respect to the L-tyrosine concentration, erroneous kinetic parameters are obtained, because a true hyperbolic dependence of the values has not been obtained. Thus, the authors working with mushroom tyrosinase, obtain a value of K M = 19.51 µM [ 10 , 11 , 12 ], when the value found for this enzyme is between 0.21 mM [ 21 ] and 0.31 mM [ 34 ]. At high pH values, K M values are constants [ 35 ].…”

“…[M] 0 values has not been obtained. Thus, the authors working with mushroom tyrosinase, obtain a value of K M = 19.51 µM [10][11][12], when the value found for this enzyme is between 0.21 mM [21] and 0.31 mM [34]. At high pH values, K M values are constants [35].…”

Exploiting HOPNO-dicopper center interaction to development of inhibitors for human tyrosinase

“…Data from published works (from mammal [62][63][64][65][66][67], bacterial [68][69][70][71] or fungal [72][73][74][75][76][77] tyrosinases) indicate that different chiral substrates show various degree of stereoselectivity on the activities / inhibition of the enzymes, but conflicting results from literature make to date the trends unreliable.…”