A. García-Jiménez, J. Teruel-Puche, C. V. Ortiz-Ruiz
Aug 1, 2016
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0
Influential Citations
15
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Journal
IUBMB Life
Abstract
4‐n‐Butylresorcinol (BR) is considered the most potent inhibitor of tyrosinase, which is why it is used in cosmetics as a depigmenting agent. However, this work demonstrates that BR is a substrate of this enzyme. The Em (met‐tyrosinase) form is not active on BR, but Eox (oxy‐tyrosinase) can act on this molecule, hydroxylating it to o‐diphenol. In turn, this is oxidized to an o‐quinone, which isomerizes to a red p‐quinone. Thus, for tyrosinase to act on this compound, a mechanism to generate Eox in the medium is required, which can be achieved by means of hydrogen peroxide or ascorbic acid. A kinetic analysis of the proposed mechanism allows its kinetic characterization: catalytic constant kcatBR (8.49 ± 0.20 s−1) and Michaelis‐constant KMBR (60.26 ± 8.76 μM). These findings are compared with those for other monophenolic substrates of tyrosinase. Studies of BR docking to the Em form of the enzyme show that the hydroxyl group in C‐1 position is oriented toward the copper atom A (CuA), as in it is L‐tyrosine. As regards Eox, BR is oriented with the carbon in C‐6 position ready to be hydroxylated. The reaction of BR originates o‐quinones, which isomerize to p‐quinones, which in turn, could react with thiol compounds, a finding that could have important implications for pharmacology and the cosmetic industry. © 2016 IUBMB Life, 68(8):663–672, 2016