Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.10.3.1 (tyrosinase)
9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine has been implicated as a potential mediating factor in a variety of neurodegenerative disorders. Dopamine can be oxidized to form a reactive dopamine quinone that can covalently modify cellular macromolecules including protein and DNA. This oxidation can be enhanced through various enzymes including tyrosinase and/or prostaglandin H synthase. One of the potential targets in brain for dopamine quinone damage is tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. The present studies demonstrated that dopamine quinone, the formation of which was enhanced through the activity of the melanin biosynthetic enzyme, tyrosinase, covalently modified and inactivated tyrosine hydroxylase. Dihydroxyphenylalanine (DOPA; the catechol-containing precursor of dopamine) also inactivated tyrosine hydroxylase under these conditions. Catecholamine-mediated inactivation occurred with both purified tyrosine hydroxylase as well as enzyme present in crude pheochromocytoma homogenates. Inactivation was associated with covalent incorporation of radiolabelled dopamine into the enzyme as assessed by immunoprecipitation, size exclusion chromatography, and denaturing sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis. Furthermore, the covalent modification and inactivation of tyrosine hydroxylase was blocked by antioxidant compounds (dithiothreitol, reduced glutathione, or NADH). In addition to kinetic feedback inhibition and the formation of an inhibitory dopamine/Fe+3 complex, these findings suggest that a third mechanism exists by which dopamine (or DOPA) can inhibit tyrosine hydroxylase, adding further complexity to the regulation of catecholamine biosynthesis.
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PMID:Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. 984 60

Oxidation of dopa and dopamine requires a net removal six electrons to produce indolequinones, the monomeric precursors of eumelanin pigment. On the other hand, their 6-fluoroderivatives suffer only four-electron oxidation to yield the same products (M. E. Rice, B. Mogaddam, C. R. Creveling, and K. L. Kirk, Anal. Chem. 59, 1534-1536, 1987). Taking advantage of this novel fluorochemistry, we reexamined the oxidative mechanism of 3,4-dihydroxyphenylacetic acid and 6-fluoro-3,4-dihydroxyphenylacetic acid to throw more light on the nature of reactive intermediates formed during the reaction. Enzymatic or chemical oxidation of 3,4-dihydroxyphenylacetic acid generated the transient o-quinone which exhibited rapid intramolecular cyclization and side chain modification to produce 2, 5,6-trihydrobenzofuran and 3,4-dihydroxymandelic acid, respectively. However, when 6-fluoro-3,4-dihydroxyphenylacetic acid was oxidized either by tyrosinase or by sodium periodate, the resultant quinone uniquely exhibited only cyclization coupled with loss of fluoride ion. This clean reaction allowed us to establish the structures of the transient reactive intermediates. Two interconvertable isomeric forms of the product were isolated and characterized from the reaction mixture. If the oxidation was carried out in water, a yellow quinolactone accumulated in the reaction mixture. This compound was instantaneously converted to a purple quinone methide upon addition of a trace amount of sodium phosphate. Passage through a C(18) HPLC column caused the reverse transformation. The structures of these products were established by semiempirical molecular orbital calculations and NMR spectrometry. Comparison of the oxidation mechanisms of melanin precursors, dopa and dopamine, with that of 3,4-dihydroxyphenylacetic acids reveals that a similar quinone methide intermediate is likely to be formed during eumelanin biosynthesis.
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PMID:Formation of a new quinone methide intermediate during the oxidative transformation of 3,4-dihydroxyphenylacetic acids: implication for eumelanin biosynthesis. 1052 94

The melanogenic marine bacterium Marinomonas mediterranea contains a multipotent polyphenol oxidase (PPO) able to oxidize substrates characteristic for tyrosinase and laccase. Thus, this enzyme shows tyrosine hydroxylase activity and it catalyzes the oxidation of a wide variety of o-diphenol as well as o-methoxy-activated phenols. The study of its sensitivity to different inhibitors also revealed intermediate features between laccase and tyrosinase. It is similar to tyrosinases in its sensitivity to tropolone, but it resembles laccases in its resistance to cinnamic acid and phenylthiourea, and in its sensitivity to fluoride anion. This enzyme is mostly membrane-bound and can be solubilized either by non-ionic detergent or lipase treatments of the membrane. The expression of this enzymatic activity is growth-phase regulated, reaching a maximum in the stationary phase of bacterial growth, but L-tyrosine, Cu(II) ions, or 2,5-xylidine do not induce it. This enzyme can be separated from a second PPO form by gel permeation chromatography. The second PPO is located in the soluble fraction and shows a sodium dodecyl sulfate (SDS)-activated action on the characteristic substrates for tyrosinase, L-tyrosine, and L-dopa, but it does not show activity towards laccase-specific substrates. The involvement of the multipotent PPO in melanogenesis and its relationship with the SDS-activated form and with the alternative functions proposed for multicopper oxidases in other microorganisms are discussed.
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PMID:Location and catalytic characteristics of a multipotent bacterial polyphenol oxidase. 1054 Oct 43

Latent mushroom tyrosinase can be considered as a zymogen when activated by proteases because the activation process fulfilled all of the kinetic dependencies predicted by a theoretical zymogen activation model previously reported. The activation was studied under two assay conditions: high and low ratio of latent tyrosinase/serine protease (trypsin and subtilisin Carlsberg) concentrations, in the presence and in the absence of a serine protease inhibitor (aprotinin). The size of the latent enzyme was 67 kDa, determined by denaturing SDS-PAGE electrophoresis and Western blot assays. After proteolytic activation, the size was 43 kDa, with an intermediate band of 58 kDa. The values of the catalytic () and Michaelis () constants for the active forms of tyrosinase resulting from the activation by subtilisin, trypsin, or sodium dodecyl sulfate on the substrate tert-butylcatechol were slightly different, which could support the idea of "one activator-one different active tyrosinase". Vacuum infiltration experiments tried to reproduce in vivo the role of mushroom serine proteases in the activation of latent tyrosinase. The use of serine protease inhibitors is proposed as a new alternative tool to prevent melanin formation.
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PMID:Kinetic study of the activation process of a latent mushroom (Agaricus bisporus) tyrosinase by serine proteases. 1055 77

This study reports the activation of a latent mushroom tyrosinase isoform by sodium dodecyl sulfate (SDS). The activation process of latent mushroom tyrosinase by SDS is characterized by the presence of a lag period (tau) prior to the attainment of a steady-state rate (V(ss)). This could be related to a slow conformational change of the latent enzyme to render the active isoform. The molecular size of the latent isoform was 67 kDa as determined by SDS-PAGE and western-blotting assays. This size did not change after activation by SDS. The molecular size of the protease-activated isoform was 43 kDa. tau and V(ss) displayed a sigmoidal relationship to the concentration of SDS, but tau was not dependent on o-diphenol or enzyme concentration. Increasing SDS concentrations decreased tau, but then lower V(ss) values were detected because of a possible excess of unfolding and subsequent denaturation of the protein. The same reaction mechanism operated in both SDS-activated and protease-activated tyrosinase isoforms despite their different kinetic features. A possible mechanism for the activation of this latent tyrosinase by SDS is proposed.
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PMID:Activation of a latent mushroom (Agaricus bisporus) tyrosinase isoform by sodium dodecyl sulfate (SDS). Kinetic properties of the SDS-activated isoform. 1055 78

A partial characterization of polyphenol oxidase (PPO) activity in raspberry fruits is described. Two early cultivars harvested in May/June (Heritage and Autumm Bliss) and two late cultivars harvested in October-November (Ceva and Rubi) were analyzed for PPO activity. Stable and highly active PPO extracts were obtained using insoluble poly(vinylpyrrolidone) (PVP) and Triton X-100 in sodium phosphate, pH 7.0 buffer. Polyacrylamide gel electrophoresis of raspberry extracts under nondenaturing conditions resolved in one band (R(f)()(1) = 0.25). Raspberry PPO activity has pH optima of 8.0 and 5.5, both with catechol (0.1 M). Maximum activity was with D-catechin (catecholase activity), followed by p-coumaric acid (cresolase activity). Heritage raspberry also showed PPO activity toward 4-methylcatechol. Ceva and Autumm Bliss raspberries showed the higher PPO activity using catechol as substrate.
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PMID:Partial characterization of polyphenol oxidase activity in raspberry fruits. 1055 67

Tyrosinase, with an isoelectric point at pH 4.9, was purified to electrophoretic homogeneity from an extremely thermophilic bacterium, Thermomicrobium roseum. Gel filtration, N-terminal amino acid sequencing and SDS/PAGE analysis indicate that T. roseum tyrosinase is composed of two identical subunits, each with a molecular mass of 43000 Da. The enzyme exhibited high substrate specificity towards catechol, chlorogenic acid, L-3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) and pyrogallol. The K(m) value of the enzyme for L-DOPA was 0.18 mM. beta-Mercaptoethanol and sodium diethyldithiocarbamate notably inhibited the enzymic activity. The activity of the enzyme was optimal at pH 9.5 and 70 degrees C, and was increased by addition of 1 mM Mg(2+), K(+) or Cu(2+). The enzyme was highly stable against high temperature and guanidine hydrochloride. The N-terminal amino acid sequence of the enzyme was determined to be Asp-Ile-Asn-Gly-Gly-Gly-Ala-Thr-Leu-Pro-Gln-Lys-Leu-Tyr. These facts indicate that T. roseum tyrosinase appears to be distinct from the tyrosinases so far purified from other sources.
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PMID:Purification and characterization of a highly stable tyrosinase from Thermomicrobium roseum. 1074 56

Tyrosinase initiates melanogenesis in a variety of organisms. The nature of melanin formed is modified subsequently by dopachrome isomerase and other melanogenic proteins. Earlier, we reported the partial purification of dopachrome isomerase (decarboxylating) from the hemolymph of Manduca sexta and demonstrated the generation of a new quinone methide intermediate during melanogenesis (Sugumaran, M., and Semensi, V. (1991) J. Biol. Chem. 266, 6073-6078). In this paper, we report the purification of this enzyme to homogeneity and a novel inhibition mechanism for regulation of phenoloxidase activity. The activity of phenoloxidase isolated from M. sexta was markedly inhibited by purified dopachrome isomerase. In turn, phenoloxidase also reciprocated by inhibiting the isomerase activity. Preformed dopaminechrome did not serve as the substrate for the isomerase; but dopaminechrome that generated in situ by phenoloxidase was readily converted to melanin pigment by the phenoloxidase/isomerase mixture. Furthermore, the isomerase, which has a molecular weight of about 40,000 in native state, exhibited retardation during affinity electrophoresis on sodium dodeyl sulfate (SDS)-polyacrylamide gel electrophoresis gel copolymerized with tyrosinase and migrated with a molecular weight of 50,000, indicating complex formation with phenoloxidase. Electrophoresis of pupal cuticular extract on polyacrylamide gel, followed by activity staining revealed the presence of a protein band carrying both phenoloxidase and isomerase activity. Accordingly, a high-molecular-weight melanogenic complex was isolated from the pharate cuticle of M. sexta. The complex catalyzed the generation of melanochrome from dopa, while the free phenoloxidase produced only dopachrome from the same substrate. When the complex was treated with trace amounts of SDS, which inhibited the activity of dopachrome isomerase present in the complex, then only the conversion of dopa to dopachrome was observed. These studies confirm the formation of a melanogenic complex between phenoloxidase and dopachrome isomerase. By forming a complex and regulating each other's activity, these two enzymes seem to control the levels of endogenous quinones.
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PMID:Insect melanogenesis. III. Metabolon formation in the melanogenic pathway-regulation of phenoloxidase activityy by endogenous dopachrome isomerase (decarboxylating) from Manduca sexta. 1086 May 57

Polyphenol oxidase (EC 1.10.3.1, PPO) in the pulp of banana (Musa sapientum L.) was purified to 636-fold with a recovery of 3.0%, using dopamine as substrate. The purified enzyme exhibited a clear single band on polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)-PAGE. The molecular weight of the enzyme was estimated to be about 41000 and 42000 by gel filtration and SDS-PAGE, respectively. The enzyme quickly oxidized dopamine, and its K(m) value for dopamine was 2.8 mM. The optimum pH was at 6.5, and the enzyme activity was stable in the range of pH 5-11 at 5 degrees C for 48 h. The enzyme had an optimum temperature of 30 degrees C and was stable even after a heat treatment at 70 degrees C for 30 min. The enzyme activity was completely inhibited by L-ascorbic acid, cysteine, sodium diethyldithiocarbamate, and potassium cyanide. Under a low buffer capacity, the enzyme was also strongly inhibited by citric acid and acetic acid at 10 mM.
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PMID:Purification and characterization of polyphenol oxidase from banana (Musa sapientum L.) pulp. 1089 14

Mytilus edulis foot protein 1 (Mefp-1) is the most well-characterized component of this sea mussel's adhesive plaque. The plaque is a condensed, heterogeneous mixture consisting of a large proportion of cross-linked biopolymers that bonds the mussel to a chosen mooring. Mefp-1 is densely populated with lysine and L-3,4-dihyroxyphenylalanine (L-dopa) residues incorporated into a repeating amino acid sequence motif. It has been proposed that one plaque cross-linking reaction is the nucleophilic addition of the epsilon-amino groups of the lysine residues into the oxidized catechol (o-diphenol) functionality (quinone) of the L-dopa residues. In order to determine if this reaction occurs in adlayers of Mefp-1, a previously developed assay for epsilon-amino groups was applied. Adlayers of Mefp-1 were exposed to an oxidant, either the enzyme, mushroom tyrosinase, or sodium periodate. Binding of alginate to adlayers was used to probe for accessibility of epsilon-amino groups. It was found that lysine residues lose the ability to bind alginate after exposure to sodium periodate, but that this loss is not clearly due to a reaction with L-dopa residues. There is a slight decrease of binding of alginate to adlayers of Mefp-1 exposed to either active or thermally deactivated mushroom tyrosinase, probably due to the obstruction of binding sites by bound enzyme. Adsorption kinetics of mushroom tyrosinase onto adlayers of Mefp-1 for active and thermally inactivated enzyme were nearly identical. Attenuated total reflection Fourier transform infrared spectroscopy was used to characterize these interactions at a germanium (Ge) interface. Copyright 2000 Academic Press.
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PMID:Influence of Sodium Periodate and Tyrosinase on Binding of Alginate to Adlayers of Mytilus edulis Foot Protein 1. 1101 42


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