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)

We have studied the serum tyrosine hydroxylase activity of tyrosinase, the key enzyme in the melanogenesis via, as a possible diagnostic factor or marker for detection, prognosis and follow-up of patients with melanoma. This activity was determined in 30 melanoma patients (MP) and in 30 healthy persons (HP) by using a radiometric method. We found mean values of 10.8+/-3.0 and 7.65+/-2.32 mU/l for serum tyrosine hydroxylase activity in MP and HP, respectively. A very significant increase in serum tyrosine hydroxylase activity was observed in MP in comparison to the enzymatic activity in HP (P < 0.00001). Although these data seem very conclusive, we wanted to know whether this test could discriminate adequately between MP and HP. In order to reach this aim, a complete statistical study was performed by using receiver operating characteristic (ROC) curve analysis. The cut-off value obtained was 8.47 mU/l. According to our results and after analytical treatment of the data, we can confirm that evaluation of tyrosine hydroxylase activity in serum could be a quick and reliable diagnostic method for detection, prognosis and follow-up in melanoma patients.
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PMID:Serum tyrosine hydroxylase activity is increased in melanoma patients. An ROC curve analysis. 971 56

B16/F10 murine melanoma cells were grown for 24 and 36 h in Dulbecco's modified Eagle medium in presence of 10-20 mM trisodium citrate. The intracellular melanin concentration and the melanin secreted in the extracellular medium was estimated. It is observed that 20 mM citrate stimulates extracellular melanin secretion in B16/F10 melanoma cells by 200% at 36 h treatment. The intracellular melanin content increased by 90%. This stimulatory effect of citrate was totally abolished when these cells were grown in presence of 1 mM phenyl thiourea, a specific inhibitor of tyrosinase activity. Citrate (0.1-5 mM) had no effect on dopa oxidase activity either at pH 5.0 or at pH 6.8. There was no increase in the tyrosinase specific activity in presence of citrate. The increased melanin synthesis was shown to be due to stimulation of cellular tyrosine hydroxylase activity by citrate. It has been suggested that enhanced melanin synthesis results in an increased production of metabolites that are toxic to the growth of melanoma cells. We have studied the effect of citrate on cellular proliferation. Following 24 and 36 h treatment with citrate, the cells exhibited a dose-dependent decrease in proliferation. In presence of 20 mM citrate the cell number was only up to 50% of the control cultures after 36 h of incubation. The growth retardation was not due to cytotoxicity. Citrate, a natural metabolite, is a unique molecule which may be involved in the regulation of melanin biosynthetic pathway, since it enhances melanogenesis by increasing the hydroxylase activity of tyrosinase which is the regulatory enzyme of this pathway. These observations add further support to the critical role of intramelanosomal pH in regulation of melanogenesis.
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PMID:In vitro modulation of proliferation and melanization of melanoma cells by citrate. 978 43

It is controversial whether tyrosinase is involved in the neuromelanin-biosynthetic pathway. We examined tyrosinase-immunoreactivity in human substantia nigra neurons which contain neuromelanin pigments, using antibodies against human tyrosinase and human tyrosine hydroxylase. In human melanoma, the antibody to tyrosinase showed intense immunoreactivity while there was no immunoreactivity with antibody to tyrosine hydroxylase. In the human midbrain pigmented neurons, however, we could detect no tyrosinase-immunoreactivity while the neurons were strongly immunoreactive to tyrosine hydroxylase. The present results suggest that tyrosinase is not involved in the main pathway of neuromelanin biosynthesis.
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PMID:Does tyrosinase exist in neuromelanin-pigmented neurons in the human substantia nigra? 979 45

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

We first identified GTP cyclohydrolase I activity (EC 3.5.4.16) in the ciliated protozoa, Tetrahymena pyriformis. The Vmax value of the enzyme in the cellular extract of T. pyriformis was 255 pmol mg-1 protein h-1. Michaelis-Menten kinetics indicated a positive cooperative binding of GTP to the enzyme. The GTP concentration producing half-maximal velocity was 0.8 mM. By high-performance liquid chromatography (HPLC) with fluorescence detection, a major peak corresponding to D-monapterin (2-amino-4-hydroxy-6-[(1'R,2'R)-1',2',3'-trihydroxypropyl]pteridin e, D-threo-neopterin) and minor peaks of D-erythro-neopterin and L-erythro-biopterin were found to be present in the cellular extract of Tetrahymena. Thus, it is strongly suggested that Tetrahymena converts GTP into unconjugated pteridine derivatives. In this study, dopamine was detected as the major catecholamine, while neither epinephrine nor norepinephrine was identified. Indeed, this protozoa was shown to possess the activity of a dopamine synthesizing enzyme, aromatic L-amino acid decarboxylase. On the other hand, activities of tyrosine hydroxylase or tyrosinase which converts tyrosine into dopa, the substrate of aromatic L-amino acid decarboxylase, could not be detected in this protozoa. Furthermore, neither dopamine beta-hydroxylase activity nor phenylethanolamine N-methyltransferase activity could be identified by the HPLC methods.
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PMID:Enzymes related to catecholamine biosynthesis in Tetrahymena pyriformis. Presence of GTP cyclohydrolase I. 985 21

Melanin pigments in lower vertebrates are often found in locations other than the skin, thus forming an extracutaneous pigmentary system of unknown function. The cellular and biochemical structure of this system is still poorly characterized. This paper deals with the ultrastructural and biochemical features of the melanogenic system of Xenopus laevis. Melanin containing cells were identified in the dorsal and ventral skin, and in the lung, spleen, liver and connective tissue surrounding blood vessels. The pigment cells in the skin and the lungs appeared to be typical melanocytes. The spleen contained isolated melanocyte-like cells, but most of the pigment cells present in this organ were associated with melanomacrophage centers. Conversely, the liver appeared devoid of melanocytes and only displayed melanomacrophage centers. Tyrosinase activity was found in all pigment-containing organs except the liver. All organs containing tyrosinase activity also displayed melanin formation potential from L-tyrosine. Therefore, tyrosine hydroxylase and melanin formation activities could be detected only in those organs containing typical melanocytes but not in locations such as the liver, where only melanomacrophages centers were found.
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PMID:The melanogenic system of Xenopus laevis. 986 45

Melanin synthesis in mammals is catalyzed by three structurally related, membrane-bound proteins, tyrosinase, and the tyrosinase-related proteins 1 and 2 (TRP1 and TRP2). Current evidence suggests that in vivo these proteins may form a multienzyme complex. However, neither the precise composition of the complex, nor the specific interactions between its components have been characterized. This study used purified preparations of tyrosinase and TRP1 to analyze their interactions in non ionic detergent solution. Purified tyrosinase and TRP1 behaved as homodimers as judged by gel filtration chromatography and electrophoresis. Upon mixing of the purified proteins, the preferential formation of heterodimers was detected by: i) coelution in gel filtration chromatography with a shift to a common partition coefficient for both proteins, and ii) the occurrence of fluorescent energy transfer between fluorescein-labeled tyrosinase and rhodamine-labeled TRP1. However, the formation of heterodimers did not cause changes in the tyrosine hydroxylase activity of the enzymes, at least under standard assay conditions. Thus, tyrosinase and TRP1 interact strongly and specifically in detergent solution to form an heterodimer that might contribute to the formation of the melanogenic complex.
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PMID:Molecular interactions within the melanogenic complex: formation of heterodimers of tyrosinase and TRP1 from B16 mouse melanoma. 991 1

Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant dams. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to L-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines.
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PMID:Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase. 1021 11

Vitiligo is a common dermatological disorder characterized by the development of complete pigment loss from focal lesions that tends to increase in size over time. The etiology of vitiligo, resulting in the disappearance of functional melanocytes from involved skin, is not clearly understood. As a consequence, no satisfactory therapy has been developed. A subtype of vitiligo, termed 'occupational' or 'contact' vitiligo, is increased in individuals who are exposed to materials containing phenolic derivatives, such as 4-tertiary butylphenol (4-TBP). Phenolic derivatives are structurally similar to tyrosine, the initial substrate of tyrosinase in the biochemical synthesis of melanin. Therefore, it has been proposed that phenolic derivatives compete with tyrosine for hydroxylation by tyrosinase and interfere with the completion of melanin synthesis and/or generate cytotoxic intermediates. Our results demonstrated that 4-TBP competitively inhibited both tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase, i.e., the first two catalytic steps in the biochemical conversion of tyrosine to melanin in cultured human melanocytes. This inhibition occurred at concentrations that did not influence the viability of melanocytes. The tyrosinase activity inhibited by 4-TBP was recovered after removing the treatment. 4-TBP did not affect the function of other enzymes, such as succinate-tetrazolium reductase, acid phosphatase and sulfatase. Since depigmentation occurred without a cytotoxic response after exposure of melanocytes to low concentration of 4-TBP, it is unclear whether the interaction between 4-TBP and tyrosinase leads to the destruction of the melanocytes in 'contact/occupational' vitiligo.
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PMID:Effects of 4-tertiary butylphenol on the tyrosinase activity in human melanocytes. 1045 91

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


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