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)

The particles of an iron hydroxide sol were found to be a suitable model for protein-oxidizing enzymes such as peroxidase and polyphenol oxidase. In addition to small molecules such as pyrogallol, human serum proteins, albumin and gamma-globulin, are shown to be substrates of the oxidizing model. The activity is markedly increased by the addition of small amounts of copper to the iron in the particles of the sol. The size and molecular weight of the enzyme model, as well as the number of active centers were determined.
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PMID:Iron hydroxide: model for enzymes that oxidize proteins. 68 84

We have observed that high SOD-like function (decomposition of superoxide anion) was observed for several iron(III) compounds with tripodal ligands and several oxovanadium(IV) compounds, and also that these compounds exhibit high catalytic activity for oxidative cleavage of 3,5-di-tert-butylcatechol in non-donating solvents such as dichloromethane or nitromethane. These are suggesting that the same reaction intermediate exists in reaction mixtures of both the SOD-like and catecholase-like functions of these compounds. Based on these facts, we have proposed a new reaction mechanism for the oxidative cleavage of catechol catalyzed by the native non-heme iron dioxygenases; this includes formation of an iron(III)-peroxide adduct as a reaction intermediate, which exhibits electrophilic nature.
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PMID:Reaction mechanism of protocatechuate 3,4-dioxygenase. 159 Aug 87

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

Kinetic experiments are reported showing that mammalian tyrosinase from B16 mouse melanoma is significantly activated by catalytic amounts of ferrous ions. Monitoring of tyrosine oxidation by both dopachrome formation and oxygen consumption showed that ferrous ions at micromolar concentrations induce a marked enzymatic activity with 0.01 U/ml of highly purified tyrosinase, whereas no detectable reaction occurs in the absence of metal over a sufficiently prolonged period of time. The extent of the activating effect, which is specific for the reduced form of iron, is proportional to the concentration of the added metal with a typical saturation profile, no further effect being observed beyond a threshold value. Changing the buffer system from phosphate to hepes or tris results in a marked decrease of the Fe2(+)-induced activation. Scavengers of active oxygen species, such as superoxide dismutase, catalase, formate and mannitol have no detectable effect on the tyrosinase activity. These results are accounted for in terms of an activation mechanism involving reduction of the cupric ions at the active site of the resting enzyme.
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PMID:Activation of mammalian tyrosinase by ferrous ions. 210 73

Insolubilizing and adhesive studies of water-soluble synthetic copoly(Tyr1 Lysx) (x = 1-10) were examined using tyrosinase in water and simulated seawater systems. Tyrosinase oxidized tyrosine aromatic nuclei, causing intermolecular crosslinking reactions, which have been assigned by the absorption band at around 360 nm. The viscosities of the model polypeptides were affected by salinity and the kinds of salts in solution systems. As a whole the amino acid compositions, salinity, system pH and beta-structure conformation are considered to play roles in the insolubilizing reaction. The bonding strengths of the model polypeptides exhibited tensile strengths of 16-24 kg/cm2 without enzyme and 29-31 kg/cm2 with tyrosinase on iron, and increased up to 10 kg/cm2 on metals by the addition of tyrosinase as an oxidant.
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PMID:Insolubilizing and adhesive studies of water-soluble synthetic model proteins. 212 88

3-Hydroxypyridine-4-ones have potential as orally active chelators of iron(III) and therefore may find application in the treatment of thalassaemia. An undesirable feature of these molecules is that they inhibit tyrosinase. We have established that alkyl substitution at position 2 in the aromatic ring minimizes interaction with tyrosinase and does so without appreciably influencing the affinity for iron(III).
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PMID:The inhibition of tyrosinase by pyridinones. 249 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

The toxicity and selectivity of 3,4-dihydroxybenzylamine (DHBA), an experimental antimelanoma agent that cannot enter the melanin pathway, broadly paralleled that of L-dopa in a panel of human melanoma cell lines sensitive or resistant to the latter drug. A human retinoblastoma cell line was found to be sensitive to both compounds. The toxicity and selectivity of both catechols were associated with inhibition of DNA synthesis; DHBA was more potent yet allowed a much greater degree of recovery compared with an equitoxic level of dopa. Dopa and DHBA had similar, dose-dependent effects on the cell cycle, arresting cells in S phase at low doses and in G1 at high doses. Replication of the DNA virus adenovirus was found to be inhibited by both agents. There was no difference between sensitive and resistant cell lines in the manganese or copper/zinc forms of superoxide dismutase, or in iron content and iron-binding capacity. Catechol toxicity was inhibited by the hydrogen peroxide scavenging agents pyruvate and methaemoglobin. Sensitivity to catechols did not correlate with melanin or tyrosinase content, rate of incorporation of tyrosine or dopa, intracellular levels of phenylalanine or tyrosine, or binding of a new monoclonal antibody directed against a melanosomal protein. These results indicate that DHBA and dopa exhibit selective toxicity for neural crest tumor cells independently of the melanisation pathway and of the superoxide scavenging system.
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PMID:Melanin synthesis and the action of L-dopa and 3,4-dihydroxybenzylamine in human melanoma cells. 290 84

Synthetic lysinoalanine (LAL) may be a more effective inhibitor of the zinc-containing enzyme carboxypeptidase A than is ethylenediamine tetraacetic acid (EDTA). The enzyme is also inactivated by alkali-treated, lysinoalanine-containing food proteins such as casein, high-lysine corn protein, lactalbumin, soy protein isolate, and wheat gluten, and by alkali-treated zein, which contains no lysinoalanine. Zinc sulfate regenerates only part of the enzymatic activity after exposure to the treated proteins. The extent of inhibition increases with protein concentration and time of treatment. Any inhibition due to phytate is distinct from that due to the treatment. Phenylethylaminoalanine (PEAA), derived from biogenic phenylethylamine, inhibited enzymatic activity of the metalloenzyme carboxypeptidase A (CPA). The inhibition was maximal at pH 7.0 in the pH range 7 to 8.5. The extent of inhibition increased with time of treatment and PEAA concentration. N-acetyl-PEAA did not inhibit the enzyme, suggesting that the free alpha-NH2 group is required for inhibition. PEAA, LAL, sodium phytate, and cysteine also inactivated the copper enzyme, polyphenol, oxidase (tyrosinase) which plays a major role in enzymatic (oxidative) browning of foods. Analogous comparative studies with LAL, EDTA, and sodium phytate suggest that the potency of PEAA as an inhibitor of CPA is similar to that of sodium phytate, and that of the four compounds tested, PEAA is least effective against tyrosinase. Related studies of the iron and copper containing enzyme cytochrome C oxidase showed that EDTA was not inhibitory, PEAA was slightly inhibitory, and LAL and sodium phytate were stronger inhibitors. Mechanistic explanations are offered to account for some of these observations. The possible relevance of these findings to in vivo protein digestion, enzymatic (oxidative) browning of foods, and the mechanism of the lysinoalanine effect on kidney cells are also discussed.
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PMID:Inactivation of metalloenzymes by lysinoalanine, phenylethylaminoalanine, alkali-treated food proteins, and sulfur amino acids. 302 44

The catalysis by iron of radical formation and subsequent oxidative damage has been well documented. Although many iron-chelating agents potentiate reactive oxygen formation and lipid peroxidation, phytic acid (abundant in edible legumes, cereals, and seeds) forms an iron chelate which greatly accelerates Fe2+-mediated oxygen reduction yet blocks iron-driven hydroxyl radical generation and suppresses lipid peroxidation. Furthermore, high concentrations of phytic acid prevent browning and putrefaction of various fruits and vegetables by inhibiting polyphenol oxidase. These observations indicate an important antioxidant function for phytate in seeds during dormancy and suggest that phytate may be a substitute for presently employed preservatives, many of which pose potential health hazards.
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PMID:Phytic acid. A natural antioxidant. 304 Jul 9


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