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)

Human melanoma cells (MM96E) were incubated with a phenotypic modifier (L-ethionine) to compare its effects on phenotypic expression with those induced by sodium butyrate and dimethyl sulfoxide. In contrast to the latter agents, L-ethionine (8mM) failed to arrest the cell cycle at the G1 phase or to inhibit colony formation ability after 48 hr incubation. Tyrosinase activity changed in parallel with 5-S-cysteinyldopa (5-S-CD) content during treatment with sodium butyrate or dimethyl sulfoxide. Tyrosinase was inhibited in L-ethionine-treated cells, probably because of metabolism of L-ethionine to sulfhydryl compounds; this remains to be clarified. Gamma-glutamyl transpeptidase activity changed inversely with tyrosinase activity after sodium butyrate or dimethyl sulfoxide incubation, whereas L-ethionine did not significantly alter the enzyme activity. In addition, only sodium butyrate induced alkaline phosphatase activity. L-ethionine was less effective than sodium butyrate or dimethyl sulfoxide in inhibiting expression of the B8G3 melanosomal antigen, as determined by Western blotting. These results suggest that phenotypic modifiers (differentiation inducers) affect melanoma cells in various ways and that melanogenesis therefore reflects only one aspect of differentiation in pigment cells.
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PMID:Alteration of melanoma melanogenesis by phenotypic modifiers. 136 29

N-t-Butyloxycarbonyl-gamma-L-glutaminyl-2-bromo-4-hydroxybenzene alpha-benzyl ester was synthesized as a precursor to gamma-L-glutaminyl-4-hydroxy[2-3H]benzene. With this labeled compound and the previously synthesized gamma-L-glutaminyl-4-hydroxy[3,5-3H]benzene, the stoichiometry of ring substitution was determined for the tyrosinase-catalyzed metabolic pathway of Agaricus bisporus. In this pathway, gamma-L-glutaminyl-4-hydroxybenzene is hydroxylated to gamma-L-glutaminyl-3,4-dihydroxybenzene which is oxidized to gamma-L-glutaminyl-3,4-benzoquinone and a compound of previously unknown structure, "490." The results indicated that the "490" quinone was derived from gamma-L-glutaminyl-3,4-benzoquinone without further ring substitution. A base-catalyzed, nonenzymatic reaction of gamma-L-glutaminyl-3,4-benzoquinone was observed which yielded a compound with a 490 nm chromophore. gamma-Glutamyl transpeptidase cleavage of gamma-L-glutaminyl-3,4-dihydroxybenzene led to the release of 4-aminocatechol which air-oxidized to a compound with identical spectral properties to "490." The structure of "490" was thus determined to be 2-hydroxy-4-imino-2,5-cyclohexadiene-1-one(2-hydroxy-4-iminoquinone). The tyrosinase-catalyzed hydroxylation of gamma-L-glutaminyl-4-hydroxybenzene was found to be optimal at pH 8.0, while the enzymatic oxidation of gamma-L-glutaminyl-3,4-dihydroxybenzene was optimal at pH 6.0.
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PMID:The metabolic pathway catalyzed by the tyrosinase of Agaricus bisporus. 610 90

gamma-L-Glutaminyl-4-hydroxybenzene is converted by the tyrosinase of the common mushroom, Agaricus bisporus, to the toxic, dormancy-inducing metabolite 2-hydroxy-4-imino-2,5-cyclohexadiene-1-one. Hydroxylation of gamma-L-glutaminyl-4-hydroxybenzene by mammalian tyrosinase was monitored by determining tritium water release from gamma-L-glutaminyl-[3,5-(3)H[4-hydroxybenzene and occurred at only 25% of the rate found with tyrosine. The dihydroxy product of the hydroxylation reaction, gamma-L-glutaminyl-3,4-dihydroxybenzene, was not oxidized by the mammalian enzyme. Therefore, oxidation of gamma-L-glutaminyl-4-hydroxybenzene to sulfhydryl-reactive quinones by mammalian tyrosinase is an unlikely explanation for the hair depigmentation and inhibition of melanocarcinoma growth observed following administration of this compound. Cleavage of gamma-L-glutaminyl-4-hydroxybenzene by gamma-glutamyl transpeptidase releasing p-aminophenol was demonstrated. p-Aminophenol was an active depigmenting and melanocytotoxic compound. N2-Methyl-gamma-L-glutaminyl-4-hydroxybenzene was synthesized, differing from gamma-L-glutaminyl-4-hydroxybenzene only by the presence of a methylated amide linkage. This chemical modification resulted in a compound resistant to cleavage by gamma-glutamyl transpeptidase and lacking in melanocytotoxic activity. gamma-Glutamyl transpeptidase cleavage is proposed as the route for transformation of gamma-L-glutaminyl-4-hydroxybenzene into an active inhibitor of melanocytes.
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PMID:Melanocytotoxicity and the mechanism of activation of gamma-L-glutaminyl-4-hydroxybenzene. 610 21

Gamma-glutamyl transpeptidase (GGT), an enzyme of the gamma-glutamyl cycle, was demonstrated in 3 of 6 cell lines derived from a single B16 murine melanoma. Its activity in these cells varied a great deal, appeared to be correlated with the developmental cycle of the cells, and was greatest in young, actively melanogenic cells. Generally, the activity seemed parallel to that of tyrosinase, an enzyme specific for melanin synthesis. The levels of both enzymes tended to decline with prolonged in vitro cultivation, but could be readily renewed after one animal passage. The 3 cell lines that were GGT-negative were nonpigmented and DOPA-negative; so was a nonmelanogenic and nonmelanocytic rhesus cell line. Melanocyte-stimulating hormone (MSH) and theophylline both enhanced pigmentation in murine melanoma cells. The mechanisms of their action apparently differed. We found that theophylline increased both DOPA- and GGT- reactive cells, whereas MSH only increased DOPA-reactive cells. All 3 GGT-positive lines were tumorigenic, and 2 GGT-negative line were not tumorigenic. Our observations suggest that GGT plays a role in the melanin biosynthetic pathway and the its activity is greater in melanoma cells that are tumorigenic.
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PMID:Theophylline and melanocyte-stimulating hormone effects on gamma-glutamyl transpeptidase and DOPA reactions in cultured melanoma cells. 612 37

Gamma-glutamyl transpeptidase (gamma-GT), an ectoenzyme involved mainly in glutathione metabolism, is expressed in B16 melanoma cells. B16 melanoma cells under continuous culture conditions show a phenotypic drift from melanotic to amelanotic and re-melanotic stages. We have investigated the regulation of gamma-GT in B16 melanoma cells under such different pigmentary conditions. High levels of gamma-GT messenger RNA (mRNA) and activity were detected in pigmented B16 melanoma cells, whereas in amelanotic B16 melanoma cells the levels were very low. Treatment with lactic acid, a known inhibitor of tyrosinase gene expression, also led to the down-regulation of gamma-GT mRNA and activity. Thus our results indicate that gamma-GT regulation depends on the pigmentation status in pigment cells. We have also assessed the levels of gamma-GT in normal murine melanocytes (melan-a cells). It was seen that melan-a cells express very low levels of gamma-GT. As gamma-GT is known to be regulated in a tissue-specific manner, and is expressed from as many as six promoters giving rise to six different types of mRNAs each having unique 5' ends, we have further investigated the type of gamma-GT mRNA expressed in B16 melanoma and melan-a cells. In this study, we have conclusively demonstrated that type I mRNA transcript of gamma-GT is expressed in B16 melanoma and melan-a cells.
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PMID:Type I gamma-GT mRNA is expressed in B16 melanoma and levels correlate with pigmentation. 1221 93