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)

Transplantable mouse melanomas possess a melanotropin-sensitive adenylate cyclase system which is responsive to alpha-melanotropin, beta-melanotropin, adrenocorticotropin (ACTH) and prostaglandin E1. It was found that sensitivity to ACTH was not directed towards the ACTH activity but to the intrinsic melanotropin activity of the ACTH molecule. Therefore, the melanotropin-sensitive adenylate cyclase system is hormonally specific to the intrinsic melanotropin activity of peptide hormones and is unique in the melanoma tissue. The significance of the sensitivity to prostaglandin E1 is obscure at present. The melanotropin-sensitive adenylate cyclase requires the presence of Mg2+ or Mn2+, for its enzymic activity. Ca2+ inhibit the enzyme in the presence of a wide range of concentrations of Mg2+. The enzymic activity is ATP concentration-dependent and the saturation concentration appears to be 1 mM. The enzyme is very labile in the unfractionated tumor homogenates. A washed 11000 X g particulate fraction, representing about 30-60% of the total enzymic activity, was found to be more stable and could be stored at 5 degrees C for 2 h without appreciable loss of the activity. This fraction retained sensitivity to melanotropin, prostaglandin E1 and NaF. About 20% of the activity of the tumor homogenate could not be sedimented by centrifugation at 105000 X g for 60 min. This "soluble" fraction was not responsive to melanotropin, prostaglandin E1 and NaF and might be a degradative product produced by the fractionation. Cyclic AMP and alpha-melanotropin were able to increase the tyrosinase activity of isolated mouse melanoma-cells in vitro under the same conditions.
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PMID:PHrmonal specificity of the melanotropin-sensitive adenylate cyclase of mouse melanoma and effect of cyclic AMP on the tyrosinase activity of mouse melanoma cells, in vitro. 0 31

Dopachrome tautomerase (DT) (EC 5.3.2.3) is a melanocyte-specific, membrane-associated, heat-labile, non-dialyzable, protease-sensitive factor which catalyzes the isomeric rearrangement of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA), apparently through a tautomerization reaction. Metal ions such as Cu, Ni, Co, Zn, Mn, Ca, Al, and Fe can also catalyze the dopachrome/DHICA isomerization. How is the reaction regulated in vivo? An attractive possibility would be that DT is a metalloenzyme. Here we present evidence that this may indeed be the case. Purified preparations of DT and tyrosinase, obtained from Cloudman S91 mouse melanoma cells, were assayed in the presence of a variety of metal chelators including EDTA (predominantly Ca and Mg), EGTA (predominantly Ca), phenylthiourea (PTU) (predominantly Cu), 2,2'-dipyridyl (predominantly Fe); 1,10-phenanthroline (predominantly Fe), and 2,3-dihydroxybenzoic acid (predominantly Fe). In addition, DT activity was assayed in the presence of two non-chelating structural analogs of 1,10-phenanthroline. Results were as follows: (i) iron chelators inhibited DT activity with no effects on tyrosinase activity; (ii) inhibition by the chelators was reversible with the addition of ferrous iron; (iii) 1,10-phenanthroline pre-complexed to ferrous iron was not inhibitory to DT; (iv) non-chelating analogs of phenanthroline were not inhibitory to DT; (v) PTU was inhibitory to tyrosinase but not DT; (vi) Ca2+ and Mg2+ chelators had little effect on either enzyme activity. Finally, studies with glycosylation inhibitors, glycosylase enzymes, and immobilized lectins, indicated that DT is a glycoprotein. The results suggest that DT is a metal-containing glycosylated enzyme, possibly with ferrous iron at its catalytic center.
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PMID:Evidence that dopachrome tautomerase is a ferrous iron-binding glycoprotein. 163 43

Electron spin resonance spectroscopy has been used to detect, characterize, and to infer structures of o-semiquinones derived from stilbene catechol estrogens. Radicals were generated enzymatically using tyrosinase and were detected as their Mg2+ complexes. It is suggested that initial hydroxylation of stilbene estrogen gives a catechol estrogen in situ; subsequent two-electron oxidation of the catechol to the quinone, followed by reverse disproportionation, leads to the formation of radicals. Consistent with this mechanism, o-phenylenediamine, a quinone trapping agent, inhibits formation of o-semiquinones. A competing mechanism of radical production involves autoxidation of the catechol. Hydroxyl radicals are shown to be produced in this system via a mechanism involving reduction of iron and copper complexes by stilbene catechols. Possible differences in the reactivity of stilbene ortho- and para-semiquinones are discussed.
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PMID:Characterization of semiquinone free radicals formed from stilbene catechol estrogens. An ESR spin stabilization and spin trapping study. 254 80

Electron spin resonance spectroscopy has been used to demonstrate production of semiquinone free radicals from the oxidation of the catechol estrogens 2- and 4-hydroxyestradiol and 2,6- and 4,6-dihydroxyestradiol. Radicals were generated by horseradish peroxidase/H2O2 or tyrosinase/O2, or by autoxidation, and were detected as their complexes with spin-stabilizing metal ions (Zn2+ and/or Mg2+). Radical production occurs via one- or two-electron oxidation of catechol estrogens, depending on the type of activating system. Autoxidation of catechol estrogens produces superoxide and H2O2 at physiological pH values. The present results also indicate a difference in the reactivity of quinones derived from 2- and 4-hydroxyestradiol. The toxicological significance of these reactions is discussed.
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PMID:An electron spin resonance study of free radicals from catechol estrogens. 301 66

Electron spin resonance spectroscopy has been used to demonstrate production of semiquinone-free radicals from the oxidation of the catechol estrogens 2- and 4-hydroxyestradiol and 2,6- and 4,6-dihydroxyestradiol. Radicals were generated either enzymatically (using horseradish peroxidase-H2O2 or tyrosinase-O2) or by autoxidation, and were detected as their complexes with spin-stabilizing metal ions (Zn2+ and/or Mg2+). In the peroxidase system, radicals are produced by one-electron oxidation of the catechol estrogen and their decay is by a second-order pathway, consistent with their disproportionation to quinone and catechol products. With tyrosinase-O2, radical generation occurs indirectly. Initial hydroxylation of phenolic estrogen (at either the 2- or 4-position) gives a catechol estrogen in situ; subsequent two-electron oxidation of the catechol to the quinone, followed by reverse disproportionation, leads to the formation of radicals. A competing mechanism for radical production involves autoxidation of the catechol. Results obtained from the estrogen systems have been compared with those from the model compound 5,6,7,8-tetrahydro-2-naphthol.
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PMID:An electron spin resonance study of o-semiquinones formed during the enzymatic and autoxidation of catechol estrogens. 609 35

The effect of Ca2+, Cd2+, Cu2+, Mg2+ and Zn2+ as acetates (10(-3) - 10(-5)M) and of 2% DMSO on the proliferation and differentiation of clone M3 of the Cloudman S91 mouse melanoma was studied and compared with the behaviour of GPK (keratocyte) and MRC5 (fibroblast) cell lines. Whereas neither calcium nor magnesium ions influenced the proliferation of the cells as measured by [3H]-thymidine incorporation, absorbance at 280 nm of NaOH cell digests and cell counts, cadmium, zinc and copper ions selectively inhibited the melanoma line. Cd2+ (10(-5)M) and Zn2+ (10(-4)M) were selectively cytotoxic to melanoma cells in contrast to keratocytes and fibroblasts. No direct effect of the cations on melanogenesis, as estimated from the ratio of absorbance at 350 nm and 280 nm and by tyrosinase assays, was demonstrated. DMSO stimulated melanogenesis in melanoma cells but inhibited their growth. Experiments with ouabain indicate that active transport is involved in the uptake of zinc by melanoma cells.
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PMID:The effect of divalent cations on Cloudman melanoma cells. 668 80

Using L-dihydroxyphenylalanine (L-DOPA) as a specific substrate, phenoloxidase (PO) from clam (Ruditapes philippinarum) was purified by Q Sepharose Fast Flow ion-exchange chromatography and Sephacryl S-100 gel-filtration, and characterized biochemically and enzymatically in this study. The molecular mass of PO in SDS-PAGE is about 76.9 kDa, and the prophenoloxidase (proPO) molecule, isolated as a monomeric protein, is 84.1 kDa. The PO molecule had a high oxidative activity, and the proPO molecule had almost no oxidative activity. The PO activity was optimal at pH 7.0 and temperature of 40 degrees C. The Km value of the PO for L-DOPA was 2.2 mmol l(-1). The PO was extremely sensitive to benzoic acid and sodium sulfite, very sensitive to citric acid, thio urea, 1-phenyl-2-thiourea and cysteine, but not sensitive to ascorbic acid. Combined with its specific enzyme activity on tyrosine and L-DOPA, it can be concluded that the Ruditapes PO is probably a kind of tyrosinase-type phenoloxidase. The PO activity was strongly inhibited by ethylenediaminetetraacetic acid (EDTA), diethyldithiocarbamate (DETC), Zn2+, Ca2+ and Cu2+, as well as by Mg2+. The results with EDTA, DETC, and some metal ions, combined with the perfect recovery effect of Cu2+ on DETC-inhibited PO activity, indicate that Ruditapes PO is most probably a copper-containing metalloenzyme.
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PMID:Purification and characterization of phenoloxidase from clam Ruditapes philippinarum. 1545 Sep 69