Hydrogen Peroxide Helps in the Identification of Monophenols as Possible Substrates of Tyrosinase

Garcia-Molina, Mary; Muñoz‐Muñoz, José Luis; BERNA, Joseph; Rodríguez-López, JoséNeptuno; Varón, R.; Garcı́a-Cánovas, Francisco

doi:10.1271/bbb.130500

Cited by 20 publications

(18 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and Supporting Information Fig. 1SI suggests that this compound is another alternative substrate of tyrosinase , rather than inhibitor or inactivator. It was therefore decided to test the possible activity of tyrosinase on BR.…”

Section: Resultsmentioning

confidence: 96%

“…In this way, the characteristic lag period of the monophenolase activity which complicates the measurement of the V 0 was eliminated. This quantity is given by the equation Finally, the activity of tyrosinase on BR as substrate was measured in the presence of (a) ascorbic acid, (b) hydrogen peroxide, and (c) catalytic concentrations of TBC and NADH as reductant to maintain the concentration of o-diphenol constant in the medium, ensuring the continuous generation of the enzymatic form E ox (17)(18)(19). Recordings were made at 480 nm, the wavelength at which the quinone of BR absorbs.…”

Section: Figmentioning

confidence: 99%

See 1 more Smart Citation

4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase

et al. 2016

View full text Add to dashboard Cite

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 E m (met-tyrosinase) form is not active on BR, but E ox (oxy-tyrosinase) can act on this molecule, hydroxylating it to o-diphenol. In turn, this is oxidized to an oquinone, which isomerizes to a red p-quinone. Thus, for tyrosinase to act on this compound, a mechanism to generate E ox 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 k BR cat (8.49 6 0.20 s 21 ) and Michaelis-constant K BR M (60.26 6 8.76 lM). These findings are compared with those for other monophenolic substrates of tyrosinase. Studies of BR docking to the E m 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 E ox , 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. , initial p-quinone formation rate; V p2Q max , maximum action rate of tyrosinase on 4-n-butylresorcinol

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Figmentioning

confidence: 99%

4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The action of the enzyme on α and β-arbutin, respectively, in the presence of H 2 O 2 [46] is shown in S6 and S6 Inset Fig. It can be observed that there is catalytic activity on these compounds, in the same way as happens with other alternative substrates [2,9,10].…”

Section: Resultsmentioning

confidence: 99%

“…However, taking into account the action mechanism of the enzyme on monophenols, the action of tyrosinase can be facilitated in the presence of an o -diphenol or H 2 O 2 , which transform E m into E ox . Therefore, the possible reaction of tyrosinase on α and β-arbutin in the presence of H 2 O 2 must be taken into account to confirm the nature of these substrates [46]. …”

Section: Methodsmentioning

confidence: 99%

Action of tyrosinase on alpha and beta-arbutin: A kinetic study

et al. 2017

View full text Add to dashboard Cite

The known derivatives from hydroquinone, α and β-arbutin, are used as depigmenting agents. In this work, we demonstrate that the oxy form of tyrosinase (oxytyrosinase) hydroxylates α and β-arbutin in ortho position of the phenolic hydroxyl group, giving rise to a complex formed by met-tyrosinase with the hydroxylated α or β-arbutin. This complex could evolve in two ways: by oxidizing the originated o-diphenol to o-quinone and deoxy-tyrosinase, or by delivering the o-diphenol and met-tyrosinase to the medium, which would produce the self-activation of the system. Note that the quinones generated in both cases are unstable, so the catalysis cannot be studied quantitatively. However, if 3-methyl-2-benzothiazolinone hydrazone hydrochloride hydrate is used, the o-quinone is attacked, so that it becomes an adduct, which can be oxidized by another molecule of o-quinone, generating o-diphenol in the medium. In this way, the system reaches the steady state and originates a chromophore, which, in turn, has a high absorptivity in the visible spectrum. This reaction allowed us to characterize α and β-arbutin kinetically as substrates of tyrosinase for the first time, obtaining a Michaelis constant values of 6.5 ± 0.58 mM and 3 ± 0.19 mM, respectively. The data agree with those from docking studies that showed that the enzyme has a higher affinity for β-arbutin. Moreover, the catalytic constants obtained by the kinetic studies (catalytic constant = 4.43 ± 0.33 s-1 and 3.7 ± 0.29 s-1 for α and β-arbutin respectively) agree with our forecast based on 13 C NMR considerations. This kinetic characterization of α and β-arbutin as substrates of tyrosinase should be taken into account to explain possible adverse effects of these compounds.

show abstract

“…However, such monophenols are highly susceptible to enzymatic oxidation by tyrosinase as alternative substrates. [15][16][17] Conversely, several polyphenols containing the resorcinol motif are known as potent tyrosinase inhibitors that are not susceptible to oxidation. [18][19][20][21][22] Thus, it was envisaged that the transformation of the monophenol structures of 1 and 2 into the corresponding resorcinols might lead to novel, effective, and hydrophilic tyrosinase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Rhododendrol glycosides as stereospecific tyrosinase inhibitors

Iwadate

Nihei

2015

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Rhododendrol derivatives 3-12 have been synthesized in six steps, including aldol condensation and/or trichloroacetimidate glycosylation as the key reactions. Each derivative showed effective inhibition of tyrosinase-catalyzed oxidation processes. In particular, a series of synthetic derivatives having an R-stereogenic center at C-2 proved to be more potent than their respective epimers. In addition, the glycosylation on the phenylbutanoid scaffold increased the difference in activity between the isomers. This suggests that the sugar moiety plays an important role in eliciting their potent inhibitory activity.

show abstract

Hydrogen Peroxide Helps in the Identification of Monophenols as Possible Substrates of Tyrosinase

Cited by 20 publications

References 25 publications

4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase

4-n-butylresorcinol, a depigmenting agent used in cosmetics, reacts with tyrosinase

Action of tyrosinase on alpha and beta-arbutin: A kinetic study

Rhododendrol glycosides as stereospecific tyrosinase inhibitors

Contact Info

Product

Resources

About