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)

Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector. Stable transfectants were selected by their resistance to the antibiotic G418. More than a dozen G418-resistant clones were isolated and were screened for tyrosinase expression using dopa-oxidase activity. The clone with the highest tyrosinase activity was selected and expanded for further studies. Northern blot analyses of total RNA from cells showed that the transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human melanotic melanoma cells. The melanin content of the transfected cells was dependent on the concentration of L-tyrosine in the culture medium. In addition, the growth of transfected cells was inhibited when grown in a medium containing high concentrations of L-tyrosine. These results suggest that tyrosinase activity is cytotoxic in a substrate-dependent manner. This may have far reaching therapeutic use for glioma tumours.
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PMID:Tyrosinase transfection produces melanin synthesis and growth retardation in glioma cells. 991 10

Determination of blood tyrosinase mRNA by RT-PCR and markers of tyrosinase activity (L-DOPA/L-tyrosine ratio) by HPLC have been proposed as biological tools for the detection of metastases in melanoma patients. We prospectively evaluated their significance and clinical value in a group of 30 stage III (n = 10) and IV (n = 20) melanoma patients and one with melanosis of Dubreuilh. L-DOPA/L-tyrosine ratio was elevated in 30% of stage III, 41% of stage IV patients (range: 7.5-261.0 x 10(5)) and in melanosis of Dubreuilh (184.8) (reference values: 6-16 X 10(5)). One stage III and four stage IV melanoma patients were positive for tyrosinase mRNA. In stage IV patients, tyrosinase mRNA positivity was associated with disease progression (P<0.01). The presence of tyrosinase mRNA in blood is more related to clinical status than level of melanin precursors, which probably reflects tumor burden.
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PMID:Simultaneous analysis of tyrosinase mRNA and markers of tyrosinase activity in the blood of patients with metastatic melanoma. 1034 Apr 38

By bioassay-guided fractionation using mushroom tyrosinase, p-coumaric acid was characterized as the principal tyrosinase inhibitor from the fresh leaves of Panax ginseng (Araliaceae). It inhibited the oxidation of L-tyrosine more strongly than that of L-3, 4-dihydroxyphenylalanine (L-DOPA) by this enzyme. On the basis of this finding, various related phenylpropanoid analogues were also tested in order to gain new insights into their structural criteria.
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PMID:Tyrosinase inhibitory p-coumaric acid from ginseng leaves. 1044 74

The oxidation-reduction potentials of cosmetic raw materials, showing tyrosinase inhibitory action, and phenolic compounds structurally similar to L-tyrosine were determined by cyclic voltammetry. The voltammograms obtained could be classified into 4 patterns (patterns 1-4). Pattern 1, characterized by oxidation and reduction peaks as a pair, was observed with catechol, hydroquinone or phenol, and pattern 2 exhibiting another oxidation peak in addition to oxidation and reduction peaks as a pair was found with arbutin, kojic acid, resorcinol, methyl p-hydroxybenzoate and L-tyrosine as the substrate of tyrosinase. Pattern 3 with an independent oxidation peak only was expressed by L-ascorbic acid, and pattern 4 with a reduction peak only at high potentials, by hinokitiol. The tyrosinase inhibitory activity of these compounds was also evaluated using the 50% inhibitory concentration (IC50) and the inhibition constant (Ki) as parameters. Hinokitiol, classified as pattern 4, showed the highest inhibitory activity (lowest IC50 and Ki). Hydroquinone showing the second highest activity belonged to pattern 1, which also included compounds showing no inhibition of tyrosinase activity. The inhibitory activity of compounds exhibiting pattern 2 was relatively low with Ki values being in the order of 10(-4) M. Although there was no consistent relationship between oxidation-reduction potentials and tyrosinase inhibitory action, the voltammetry data can be used as an additional index to establish the relationship between the structure and the tyrosine inhibitory activity.
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PMID:Relationship between tyrosinase inhibitory action and oxidation-reduction potential of cosmetic whitening ingredients and phenol derivatives. 1048 70

Terminal differentiation can result in either viable, non-proliferating or apoptotic cells. In B16 melanoma, millimolar L-tyrosine induces tyrosinase, a key enzyme for terminal pigmentation concurrent with either irreversible growth arrest at low cell density, or apoptosis at high cell density. Since the promoter for melanocyte-specific tyrosinase expression contains sites for the Sp1 transcription factor, we have investigated the relationship of Sp1-mediated GC-box DNA binding activity to growth control in undifferentiated and in terminally differentiated viable or apoptotic cells. Nuclear extracts from viable, differentiated cells showed increased retardation of GC box DNA sequence compared with that seen in proliferating cells or those reversibly arrested in early G(1) or late G(1) / S. In contrast, nuclear proteins from dying, differentiated cells showed loss of nuclear GC box DNA binding activity without decrease in binding to TTTGCGCG sequences recognized by the E2F transcription factor, which is known to interact with Sp1. However, cyto-plasmic fractions from apoptotic cells revealed phos-phatase-activated retardation of GC box DNA, which was not evident in similarly treated fractions from undifferentiated cells or sparse differentiated cells. Terminal differentiation also correlated with increase in a slow-migrating phosphorylated Sp1 isoform. Our data suggests that lack of nuclear Sp1/GC box DNA binding activity, may promote apoptosis by diminishing expression of survival-associated genes regulated by GC box DNA promoter sequences in dense terminally differentiated melanoma cells.
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PMID:Unequal nuclear Sp1/GC box DNA binding activity distinguishes proliferating from differentiated senescent or apoptotic cells. 1049 28

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

Despite the importance of the substrate gamma-L-glutaminyl-4-hydroxybenzene (GHB) in the melanin biosynthesis pathway in mushrooms Agaricus bisporus, the kinetics of its oxidation catalyzed by tyrosinase has never been properly characterized. For this purpose GHB and its corresponding o-diphenol (GDHB) were isolated and purified from A. bisporus mushrooms. The kinetic constants that characterize the action of tyrosinase on GHB and GDHB are = 2.10 +/- 0.10 microM/min, = 0.30 +/- 0.03 mM, = 210.0 +/- 7.3 microM/min, and = 7.80 +/- 0.41 mM. The oxygen kinetic constants for tyrosinase in the presence of these compounds are = 3. 20 +/- 0.21 microM/min, = 1.50 +/- 0.12 microM, = 200.2 +/- 8.1 microM/min, and = 100.2 +/- 8.2 microM. These values were compared to those obtained for the pair L-tyrosine/L-DOPA. The kinetic and structural reaction mechanisms of tyrosinase were corroborated for these physiological phenolic compounds.
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PMID:Kinetic study of the oxidation of gamma-L-glutaminyl-4-hydroxybenzene catalyzed by mushroom (Agaricus bisporus) tyrosinase. 1055 75

A common flavonol, kaempferol, isolated from the fresh flower petals of Crocus sativus L. (Iridaceae) was found to inhibit the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by mushroom tyrosinase with an ID(50) of 67 microgram/mL (0.23 mM). Interestingly, its 3-O-glycoside derivatives did not inhibit this oxidation. The inhibition kinetics analyzed by a Lineweaver-Burk plot found kaempferol to be a competitive inhibitor, and this inhibitory activity presumably comes from its ability to chelate copper in the enzyme. This copper chelation mechanism can be applicable for all of the flavonols as long as their 3-hydroxyl group is free. However, quercetin, kaempferol, and galangin each affect the oxidation of L-tyrosine in somewhat different ways.
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PMID:Flavonols from saffron flower: tyrosinase inhibitory activity and inhibition mechanism. 1055 77

The pigment melanin in human skin is a major defense mechanism against ultraviolet light of the sun, but darkened skin color, which is the result of increased and redistributed epidermal melanin, could be a serious aesthetic problem. Epidemiologically, it is well known that the consumption of green tea may help prevent cancers in humans and also reduce several free radicals including peroxynitrite. In the present study, to assess the efficacy of the inhibition of mushroom tyrosinase (monophenol monooxygenase EC 1.14.18.1), ten kinds of Korean traditional teas were screened for their tyrosinase inhibitory activity. Green tea was the strongest inhibitor, and the major active constituents in the tea are (-)-epicatechin 3-O-gallate (ECG), (-)-gallocatechin 3-O-gallate (GCG), and (-)-epigallocatechin 3-O-gallate (EGCG). All are catechins with gallic acid group as an active site. The kinetic analysis for inhibition of tyrosinase revealed a competitive nature of GCG with this enzyme for the L-tyrosine binding at the active site of tyrosinase.
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PMID:Inhibition of tyrosinase by green tea components. 1057 99

It was previously found that L-tyrosine oxidation product(s) are cytotoxic, genotoxic and increase the sister chromatid exchange (SCE) levels in human melanoma cells. In this work, the micronucleus assay has been performed on human melanotic and amelanotic melanoma cell lines (Carl-1 MEL and AMEL) in the presence of 1.0, 0.5 and 0.1 mM L-tyrosine concentrations to investigate if melanin synthesis intermediate(s) increase micronuclei production. L-Tyrosine oxidation product(s) increased the frequency of micronuclei in melanoma cells; 0.1 mM phenylthiourea (PTU), an inhibitor of L-tyrosine oxidation by tyrosinase, lowered the micronucleus production to the control levels. The culture of melanoma cells with high L-tyrosine in the culture medium resulted in a positive response to an ELISA-based apoptotic test. For comparison the effect of L-tyrosine on micronuclei production in human amelanotic melanoma cells was also investigated; the micronucleus production in the presence of 1 mM L-tyrosine in the culture medium was lower than that found with melanotic melanoma cells of the same cell line. The data suggest that melanin synthesis intermediates arising from L-tyrosine oxidation may cause micronuclei production in Carl-1 human melanoma cells; the addition of PTU in the presence of L-tyrosine decreased the frequency of micronuclei to about the control values thus the inhibition of melanogenesis may have some clinical implication in melanotic melanoma.
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PMID:Inhibition of L-tyrosine-induced micronuclei production by phenylthiourea in human melanoma cells. 1063 35


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