Effect of pH on the oxidation pathway of dopamine catalyzed by tyrosinase

García-Moreno, Manuela; Rodríguez-López, JoséNeptuno; Martı́nez-Ortiz, Francisco; Tudela, José; Varón, R.; Garcı́a-Cánovas, Francisco

doi:10.1016/0003-9861(91)90216-6

Cited by 58 publications

(48 citation statements)

References 29 publications

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“…Additionally, under mild acidic conditions (pH < 6), hydroxylation of dopamine quinone can occur to form 2,4,5-trihydroxyphenethylamine (topamine) and the corresponding topamine quinone undergoes Michael-type addition with a primary amine at a much slower rate than dopamine quinone. 68 Elevated stability of quinone methide under acidic conditions may also contribute to the reduced ability of PEG-D to form interfacial bonds with biological tissues. 59 …”

Section: Results and Discussionmentioning

confidence: 99%

Effect of pH on the Rate of Curing and Bioadhesive Properties of Dopamine Functionalized Poly(ethylene glycol) Hydrogels

et al. 2014

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The remarkable underwater adhesion strategy employed by mussels has inspired bioadhesives that have demonstrated promise in connective tissue repair, wound closure, and local delivery of therapeutic cells and drugs. While the pH of oxygenated blood and internal tissues is typically around 7.4, skin and tumor tissues are significantly more acidic. Additionally, blood loss during surgery and ischemia can lead to dysoxia, which lowers pH levels of internal tissues and organs. Using 4-armed PEG end-capped with dopamine (PEG-D) as a model adhesive polymer, the effect of pH on the rate of intermolecular cross-linking and adhesion to biological substrates of catechol-containing adhesives was determined. Adhesive formulated at an acidic pH (pH 5.7–6.7) demonstrated reduced curing rate, mechanical properties, and adhesive performance to pericardium tissues. Although a faster curing rate was observed at pH 8, these adhesives also demonstrated reduced mechanical and bioadhesive properties when compared to adhesives buffered at pH 7.4. Adhesives formulated at pH 7.4 demonstrated a good balance of fast curing rate, elevated mechanical properties and interfacial binding ability. UV–vis spectroscopy evaluation revealed that the stability of the transient oxidation intermediate of dopamine was increased under acidic conditions, which likely reduced the rate of intermolecular cross-linking and bulk cohesive properties for hydrogels formulated at these pH levels. At pH 8, competing cross-linking reaction mechanisms and reduced concentration of dopamine catechol due to auto-oxidation likely reduced the degree of dopamine polymerization and adhesive strength for these hydrogels. pH plays an important role in the adhesive performance of mussel-inspired bioadhesives and the pH of the adhesive formulation needs to be adjusted for the intended application.

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Section: Results and Discussionmentioning

confidence: 99%

Effect of pH on the Rate of Curing and Bioadhesive Properties of Dopamine Functionalized Poly(ethylene glycol) Hydrogels

et al. 2014

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“…We described the biosynthesis pathway of melanins from l ‐tyrosine as an enzymatic‐enzymatic‐chemical mechanism [12]. We were the first group to demonstrate the chemical generation of D and to characterize its kinetic behaviour many years ago [13,14,24–33]. However, our mechanism has always supported the idea that the oxy form of the enzyme attacks M to produce a complex, E m D, which can release free D or oxidize D to Q (Scheme 1a).…”

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confidence: 99%

Oxidation by mushroom tyrosinase of monophenols generating slightly unstable o‐quinones

Fenoll

Rodrı́guez-López

Garcı́a-Sevilla

et al. 2000

European Journal of Biochemistry

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Tyrosinase can act on monophenols because of the mixture of mettyrosinase (E m ) and oxytyrosinase (E ox ) that exists in the native form of the enzyme. The latter form is active on monophenols although the former is not. However, the kinetics are complicated because monophenols can bind to both enzyme forms. This situation becomes even more complex as the products of the enzymatic reaction, the o-quinones, are unstable and continue evolving to generate o-diphenols in the medium. In the case of substrates such as 4-methoxyphenol, 4-ethoxyphenol and 4-tert-butylphenol, tyrosinase generates o-quinones which become unstable with small constants of approximately , 10 23 s 21 . The system evolves from an initial steady state, reached when t30, through a transition state towards a final steady state, which is never reached because the substrate is largely consumed. The mechanisms proposed to explain the enzyme's action can be differentiated by the kinetics of the first steady state. The results suggest that tyrosinase hydroxylates monophenols to o-diphenols, generating an intermediate E m -diphenol in the process, which may oxidize the o-diphenol or release it directly into the medium. In the case of o-quinone formation, its slow instability generates o-diphenol which activates the enzymatic system yielding parabolic time recordings.Keywords: enzyme kinetics; monophenol; mushroom; o-diphenol; o-quinone; tyrosinase.Tyrosinase is a copper-enzyme [1,2] widely distributed throughout the phylogenetic scale [3,4] that catalyses the hydroxylation of monophenols to o-diphenols and the oxidation of the latter to o-quinones using molecular oxygen [5]. The enzyme is responsible for skin, eye, inner ear and hair melanization [6,7], and browning in fruits and vegetables [8±10]. Its action on its physiological substrate, l-tyrosine, has been studied widely and its kinetic has been largely interpreted [11±14]. Studies have also been made of its action on monophenols such as 4-hydroxyanisole (4HA), 4-ethoxyphenol (4EP) and 4-tert-butylphenol (4TBP), to produce fairly stable o-quinones [15±20]. In 1987, our group [12] proposed a kinetic mechanism based on structural aspects developed by Solomon [21] to explain the enzyme's action (Scheme 1a). Briefly, the oxy form of the enzyme (E ox ) starts the turnover by acting on the monophenol (M), which is hydroxylated to the mettyrosine± diphenol intermediate (E m D). At this point, the enzyme can oxidize D to o-quinone (Q), producing the desoxy form of the enzyme (E d ), or release D to form the met (E m ) form, which binds with M to produce the inactive form, E m M. If Q is very unstable, as occurs in the case of o-dopaquinone, D is recycled to the medium through intramolecular cyclization and further redox steps [12]. This would involve the transformation of the E m form of the enzyme (which is inactive towards M) into the E ox form (which is active towards M) giving rise to the lag time, which is a characteristic of this activity (Scheme 1a 1 b) [12±14]. In such cases the system would re...

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“…The results of this investigation demonstrate for the first time that semiquinone and quinone intermediates of eumelanin are the initial products derived from the 'OH-mediated oxidations of dopa, DA, TOPA, and 6-OHDA. Kinetic investigations concerning the oxidation chemistry of these catechols have shown pH to strongly influence these reactions (Li and Christensen, 1994;Jimenez et al, 1984;Gee and Davidson, 1985;Garcia-Moreno et al, 1991;Rodriguez-Lopez et al, 1992;Newcomer et al, 1993). At pH 6 or higher o-quinones cyclize, whereas at a lower pH they undergo hydroxylation (see Fig.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Hydroxyl Radical Attack on Dopa, Dopamine, 6‐Hydroxydopa, and 6‐Hydroxydopamine

Nappi

Vass

Prota

et al. 1995

Pigment Cell Research

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High pressure liquid chromatography with electrochemical detection (HPLC-ED) was employed in conjugation with a sensitive and specific salicylate hydroxylation assay to evaluate the immediate effects of hydroxyl radical (.OH) attack on four catechol intermediates of eumelanin, dopamine (3,4-dihydroxyphenylethylamine), its precursor dopa (3,4-dihydroxyphenylalanine), and their respective neurotoxic trihydroxyphenyl derivatives, 6-hydroxydopamine (2,4,5-trihydroxyphenylethylamine,6-OHDA) and 6-hydroxydopa(2,4,5-trihydroxyphenylalanine, TOPA). Semiquinone and quinone species were identified as the initial products of the oxidation of these four catechol substrates. The enhanced oxidations of the catechols when exposed to .OH attack was accompanied by marked decreases in the level of each semiquinone species. Quinone levels were elevated in reactions involving .OH attack on dopamine and 6-OHDA, but absent in reactions involving radical attack on dopa or TOPA, suggesting that dopaquinone (DOQ) and TOPA p-quinone (TOPA p-Q) are oxidized more rapidly by .OH than are the quinones of dopamine and 6-OHDA. The formation of 6-OHDA p-quinone (6-OHDA p-Q) in incubations involving DA and .OH suggest that the .OH-mediated hydroxylation of DA may be a mechanism for generating this potentially cytotoxic trihydroxyphenyl. The results of this study demonstrate for the first time that semiquinone and quinone intermediates of eumelanin are the initial products derived from the .OH-mediated oxidations of dopa, DA, TOPA, and 6-OHDA. These observations suggest that if .OH is generated beyond the capabilities of cytoprotective mechanisms, the radical can rapidly oxidize catechol precursors, augment melanogenesis, and generate additional cytotoxic quinoid intermediates of eumelanin.

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Effect of pH on the oxidation pathway of dopamine catalyzed by tyrosinase

Cited by 58 publications

References 29 publications

Effect of pH on the Rate of Curing and Bioadhesive Properties of Dopamine Functionalized Poly(ethylene glycol) Hydrogels

Effect of pH on the Rate of Curing and Bioadhesive Properties of Dopamine Functionalized Poly(ethylene glycol) Hydrogels

Oxidation by mushroom tyrosinase of monophenols generating slightly unstable o‐quinones

The Effects of Hydroxyl Radical Attack on Dopa, Dopamine, 6‐Hydroxydopa, and 6‐Hydroxydopamine

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