Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reaction of opioid peptides with mushroom tyrosinase in the presence of an excess of a thiol compound gives rise to cysteinyldopaenkephalins (CDEnks). The major product is represented by the 5-S-CDEnk (80%) and the minor one by the isomer 2-S-CDEnk (20%). The adducts between leucine-enkephalin (Leu-enk) and cysteine have been isolated by high performance liquid chromatography (HPLC) and identified by amino acid analysis and electrospray ion mass spectrometry. 5-S-CDEnk is able to bind to opioid receptors in bovine brain membranes. Its binding affinity is higher for delta than for mu receptors and about 8-fold lesser than that exploited by Leu-enk. In the presence of the peroxidase/H(2)O(2) system, CDEnks can be converted into the corresponding pheo-opiomelanins.
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PMID:Cysteinyldopaenkephalins: synthesis, characterization and binding to bovine brain opioid receptors. 1071 71

Exposure of the skin to certain phenols or catechols such as 4-tert-butylphenol (TBP) and 4-tert-butylcatechol (TBC) may cause leukoderma. These substances are used in the polymer industry and numerous cases have been reported. Several theories of the mechanism for chemical leukoderma have been suggested. In the present study, TBP and TBC are shown to be oxidised by tyrosinase. The oxidation of TBC yields a quinone that is further investigated on its reactions with cysteine or glutathione (GSH). The products formed are isolated and identified by mass spectrometry and nuclear magnetic resonance as being 4-tert-butyl-6-S-cysteinylcatechol (cys-TBC) and 4-tert-butyl-6-S-glutathionylcatechol (GS-TBC). The reactive quinone is a strongly electrophilic substance that rapidly reacts with GSH. A depletion of the GSH defence system may give conditions where the quinone lives long enough to effect its toxic properties. The influence of the reactive tert-butylquinone on enzymatic activities is demonstrated by the inhibition of glyceraldehyde-3-phosphate dehydrogenase.
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PMID:Tyrosinase-mediated formation of a reactive quinone from the depigmenting agents, 4-tert-butylphenol and 4-tert-butylcatechol. 1076 94

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

In a reaction between (-)-epicatechin (EC) and 2-mercaptoethanol (2ME), catalyzed by partially purified polyphenol oxidase (PPO) extracted from the style of Rhododendron mucronatum, 2'-(2-hydroxyethylthio)-(-)-epicatechin (2'-HETEC), 5'-(2-hydroxyethylthio)-(-)-epicatechin (5'-HETEC), and 2',5'-bis(2-hydroxyethylthio)-(-)-epicatechin (2',5'-HETEC) were formed. The rate of formation of 2',5'-HETEC from 5'-HETEC was faster than that from 2'-HETEC. In the absence of 2ME, the concentration of EC decreased rapidly and the reaction mixture turned brown; 2'-, 5'-, and 2',5'-HETEC, especially 2'-substituted HETECs. reacted more slowly. These data indicate that 2ME acts both as an inhibitor of the polymerization of O-quinone, presumably by binding to it and as a reductant involved in the conversion of O-quinone to O-dihydroxyphenol, Inhibition of enzymatic browning by other thiol compounds such as cysteine and dithiothreitol was also investigated.
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PMID:Inhibition of enzymatic browning and protection of sulfhydryl enzymes by thiol compounds. 1093 51

Eumelanogenesis and phaeomelanogenesis diverge at an early stage in pigment formation, namely at the point where dopaquinone, the initial product of tyrosine oxidation by tyrosinase, undergoes one of two types of reaction: either (1) a reductive endocyclisation in which a Michael addition of the side-chain amino group takes place; or (2) a reductive addition of cysteine to give cysteinyldopa. In the former case, the product cyclodopa, is known rapidly to undergo a redox exchange reaction with dopaquinone to yield dopachrome, the precursor of the eumelanogenic pathway. In the second instance, cysteinyldopa is regarded as leading to the formation of benzothiazoles, which are characteristic of phaeomelanin. The precursor molecule of the phaeomelanic pathway is cysteinyldopaquinone. We have examined quantitatively the role of dopaquinone in the non-enzymatic oxidation of 5-S-cysteinyldopa using pulse radiolysis and have demonstrated that the redox exchange reaction between dopaquinone and 5-S-cysteinyldopa occurs spontaneously with a rate constant of 8.8 x 10(5) M(-1) sec(-1). This study has also enabled an improved estimate of < or = 4 x 10(7) M(-1) sec(-1) to be obtained for the rate constant of the reaction of dopaquinone with cyclodopa. Calculations utilising these figures and estimates of the rate constants for the other reactions in early melanogenesis, demonstrate that, whilst similar pathways are invoked, the phaeomelanic pathway predominates in the presence of cysteine, irrespective of the availability of dopaquinone and thus independently of the rate of tyrosinase-catalysed oxidation. This suggests that the balance between the formation of eumelanin and phaeomelanin is regulated principally by the availability of cysteine at the site of melanogenesis.
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PMID:Spontaneous redox reactions of dopaquinone and the balance between the eumelanic and phaeomelanic pathways. 1095 95

The polyphenol oxidase from field bean (Dolichos lablab) seeds has been purified to apparent homogeneity by a combination of ammonium sulfate precipitation, DEAE-Sephacel chromatography, phenyl agarose chromatography, and Sephadex G-200 gel filtration. The purified enzyme has a molecular weight of 120 +/- 3 kDa and is a tetramer of 30 +/- 1.5 kDa. Native polyacrylamide gel electrophoresis of the purified enzyme revealed the presence of a single isoform with an observed pH optimum of 4.0. 4-Methyl catechol is the best substrate, followed by catechol, and L-3,4-dihydroxyphenylalanine, all of which exhibited a phenomenon of inhibition by excess substrate. No activity was detected toward chlorogenic acid, catechin, caffeic acid, gallic acid, and monophenols. Tropolone, both a substrate analogue and metal chelator, proved to be the most effective competitive inhibitor with an apparent K(i) of 5.8 x 10(-)(7) M. Ascorbic acid, metabisulfite, and cysteine were also competitive inhibitors.
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PMID:Purification and characterization of a polyphenol oxidase from the seeds of field bean (Dolichos lablab). 1099 79

Melanins are difficult to characterize because of their intractable chemical properties, the heterogeneity in their structural features, and the lack of methods to split melanin polymers into monomer units. To overcome this difficulty, we developed a rapid and sensitive method for quantitatively analyzing eumelanin and pheomelanin in biological samples that is based on the formation of pyrrole-2,3,5-tricarboxylic acid and/or aminohydroxyphenylalanine followed by HPLC determination. The method has been applied to the study of melanogenesis. The results summarized in this review are: 1) Biochemical studies show that in the process of mixed melanogenesis, cysteinyldopas are produced first, which are then oxidized to give pheomelanin; following cysteine depletion, eumelanin is then deposited on the preformed pheomelanin. 2) In vitro and in vivo studies show that tyrosinase activity is the most important factor that regulates the switch of melanogenesis, with lower tyrosinase activities favoring pheomelanogenesis; further suppression of melanogenesis results in a lack of pigment production. 3) In cultured melanocytes, the concentrations of tyrosine and cysteine, and their ratio in the medium, are important in determining the concentrations of eumelanin and pheomelanin produced and their ratio in the cells. In conclusion, our HPLC microanalytical method for characterizing eumelanin and pheomelanin has become a useful tool for the study of melanogenesis.
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PMID:Chemical analysis of melanins and its application to the study of the regulation of melanogenesis. 1104 66

The intracellular vesicular trafficking in the melanosome biogenesis (melanogenesis) is reviewed with the incorporation of our own experimental findings. The melanosome biogenesis involves four stages of melanosome maturation, which reflect the transport of structural and enzymatic proteins from Golgi (trans-Golgi network: TGN) to the melanosomal compartment and their organization therein. The major melanosomal proteins include tyrosinase gene family protein (tyrosinase and tyrosinase-related protein; TRP), lysosome-associated membrane protein (Lamp) and gp100 (pmel 17). They are glycosylated in the endoplasmic reticulum, and transported by vesicles from the TGN to the melanosomal compartment. During the formation of transport vesicles, they assemble on the cytoplasmic face of the TGN to select cargo by interacting directly or indirectly with coat proteins. Tyrosinase and TRP-1 possess the dileucine motifs at the cytoplasmic domain, to which adapter protein-3 binds to transport them from the TGN to stage I melanosomes (related to late endosomes) and then to stage II melanosomes. A number of small guanosine triphosphate-binding proteins, including rab 7, appear to be involved in this vesicular transport. Phosphatidyl inositol 3 kinase also regulates this membrane trafficking of melanosomal glycoprotein. Eumelanogenesis is controlled by melanocyte-stimulating hormone, and all three tyrosinase gene family proteins are transported from the TGN to stage II melanosomes that are elliposoidal and contain the structural matrix of filaments/lamellae. In contrast, pheomelanogenesis is primarily regulated by agouti signal protein, and only tyrosinase is transported from stage I melanosomes to stage II melanosomes that are spherical and related to lysosomes. Because of the absence of TRP-1 and TRP-2 in pheomelanogenesis, it may be suggested that tyrosinase is involved in lysosomal degradation after forming dopaquinone, to which the cysteine present in the lysosomal granule binds to form cysteinyldopas that will then be auto-oxidized to become pheomelanin.
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PMID:Intracellular vesicular trafficking of tyrosinase gene family protein in eu- and pheomelanosome biogenesis. 1104 67

UV-induced melanogenesis is a well known physiological response of human skin exposed to solar radiation; however, the signaling molecules involved in the stimulation of melanogenesis in melanocytes following UV exposure remain unclear. In this study we induced melanogenesis in vitro in normal human epidermal melanocytes using a single irradiation with UVA at 1 kJ/m2 and examined the potential involvement of mitogen-activated protein kinases (MAPK) as UVA-responsive signaling molecules in those cells. UVA irradiation did not affect the proliferation of melanocytes, but it did increase tyrosinase mRNA expression, which reached a maximum level 4 hr after UVA irradiation. The amount of tyrosinase protein, as quantitated by immunoblotting, was also increased at 24 hr following UVA irradiation. Among the MAPK examined, extracellular signal-related kinase (ERK) 1/2 was phosphorylated within 15 min of UVA irradiation, but no such phosphorylation was observed for c-Jun N-terminal kinases (JNK) or p38. Accordingly, the activity of ERK1/2 was also increased shortly after UVA irradiation. These responses of ERK1/2 to UVA irradiation were markedly inhibited when cells were pre-treated with N-acetyl-L-cysteine, an antioxidant, or with suramin, a tyrosine kinase receptor inhibitor. The formation of (6-4)photoproducts or cyclobutane pyrimidine dimers was not detected in cellular DNA after UVA irradiation. These findings suggest that a single UVA irradiation-induced melanogenesis is associated with the activation of ERK1/2 by upstream signals that originate from reactive oxygen species or from activated tyrosine kinase receptors, but not from damaged DNA.
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PMID:Possible involvement of ERK 1/2 in UVA-induced melanogenesis in cultured normal human epidermal melanocytes. 1131 Jul 89

Polyphenol oxidase (EC 1.10.3.1, o-diphenol: oxygen oxidoreductase, PPO) of banana (Musa sapientum L.) peel was partially purified about 460-fold with a recovery of 2.2% using dopamine as substrate. The enzyme showed a single peak on Toyopearl HW55-S chromatography. However, two bands were detected by staining with Coomassie brilliant blue on PAGE: one was very clear, and the other was faint. Molecular weight for purified PPO was estimated to be about 41 000 by gel filtration. The enzyme quickly oxidized dopamine, and its Km value (Michaelis constant) for dopamine was 3.9 mM. Optimum pH was 6.5 and the PPO activity was quite stable in the range of pH 5-11 for 48 h. The enzyme had an optimum temperature at 30 degrees C and was stable up to 60 degrees C after heat treatment for 30 min. The enzyme activity was strongly inhibited by sodium diethyldithiocarbamate, potassium cyanide, L-ascorbic acid, and cysteine at 1 mM. 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:Partial purification and characterization of polyphenol oxidase from banana (Musa sapientum L.) peel. 1131 78


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