Action of ellagic acid on the melanin biosynthesis pathway

•Ellagic acid is not an inhibitor but an alternative substrate of tyrosinase.•The Michaelis and catalytic constants of ellagic acid are 138 μM and 0.471 s−1.•Ellagic acid partly inhibits the melanogenesis process through its antioxidant power.•Ellagic acid reacts with o-quinones and semiquinones in the melanogenesis pathway.

BackgroundTyrosinase is an enzyme involved in the first steps of the melanogenesis process. It catalyzes the hydroxylation of monophenols to o-diphenols and the oxidation of the latter to o-quinones. Ellagic acid (EA) is a phenolic compound which has been described as a tyrosinase inhibitor and is used in the cosmetic industry as a whitening agent. However, it has hydroxyl groups in ortho position and could act as a substrate rather than inhibitor. This aspect should be taken into consideration when using this compound as a cosmetic ingredient due to the reactive character of o-quinones.ObjectiveTo determine whether ellagic acid is a substrate or an inhibitor of tyrosinase, to characterize it kinetically and interpret its role in the melanogenesis process.MethodsUV–vis spectrophotometry was used to follow the action of tyrosinase on typical substrates and ellagic acid. A chronometric method was chosen for the kinetic characterization of ellagic acid.ResultsEllagic acid is not an inhibitor per se but an alternative substrate of tyrosinase. It is oxidized by the enzyme to an unstable o  -quinone. Its kinetic characterization provided low Michaelis and catalytic constants (KMEA = 138 ± 13 μM and kcatEA = 0.47 ± 0.02 s−1). Furthermore, ellagic acid, which is a powerful antioxidant, may chemically reduce the o-quinones (o-dopaquinone) and semiquinones, in this way inhibiting the melanogenesis.ConclusionEllagic acid is oxidized by tyrosinase, producing reactive o-quinones. As an antioxidant it can inhibit the melanogenesis process. This first aspect should be taken into consideration in its application as a cosmetic ingredient due to the toxicity of o-quinones and its ability to modify the redox status of the cell.