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 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

1. Under defined conditions, the hydroxylation of p-coumaric acid catalysed by a phenolase from leaves of spinach beet (Beta vulgaris L.) was observed to develop its maximum rate only after a lag period. 2. By decreasing the reaction rate with lower enzyme concentrations or by increasing it with higher concentrations of reductants, the length of the lag period was inversely related to the maximum rate subsequently developed. 3. Low concentrations of caffeic acid or other o-dihydric phenols abolished this lag period. With caffeic acid, the rate of hydroxylation was independent of the reductant employed. 4. Hydroxylation was inhibited by diethyldithiocarbamate, but with low inhibitor concentrations hydroxylation recovered after a lag period. This lag could again be abolished by the addition of high concentrations of caffeic acid or other o-dihydric phenols. 5. Catechol oxidase activity showed no lag period, and did not recover from diethyldithiocarbamate inhibition. 6. The purified enzyme contained 0.17-0.33% copper; preparations with the highest specific activity were found to have the highest copper content. 7. The results are interpreted to suggest that the oxidation of o-dihydric phenols converts the enzymic copper into a species catalytically active in hydroxylation. This may represent the primary function for the catechol oxidase activity of the phenolase complex. The electron donors are concerned mainly, but not entirely, in the reduction of o-quinones produced in this reaction.
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PMID:The action of o-dihydric phenols in the hydroxylation of p-coumaric acid by a phenolase from leaves of spinach beet (Beta vulgaris L.). 499 65

The metabolic pathways of dietary flavonoids are still largely unknown. In the present work, mass spectrometry and UV-vis spectroscopy studies were used to show that the naturally occurring flavonoid catechin underwent enzymatic oxidation by tyrosinase in the presence of glutathione (GSH) to form mono-, bi-, and tri-glutathione conjugates of catechin and mono- and bi-glutathione conjugates of a catechin dimer. A hydroxylated catechin adduct was also detected. Using UV spectroscopy, it was shown that the catechol B-ring of catechin was oxidized by tyrosinase to form an o-quinone which could be reduced back to catechin with potassium borohydride or reacted with GSH to form glutathione conjugates. The catechin-glutathione conjugates formed had much lower distribution coefficient values than catechin itself. When peroxidase and hydrogen peroxide were used instead of tyrosinase, only mono-glutathione conjugates were formed but not bi-glutathione conjugates or hydroxylated adducts. (1)H NMR evidence showed that three different mono-glutathione conjugates on ring B of catechin were formed by peroxidase and hydrogen peroxide. Rat liver microsomes and NADPH or cumene hydroperoxide also catalyzed catechin-glutathione conjugate formation which was prevented by benzylimidazole, a P450 2E1 inhibitor. Catechin cytotoxicity toward isolated hepatocytes was also markedly enhanced by hydrogen peroxide or cumene hydroperoxide and was prevented by benzylimidazole, suggesting that catechin could be metabolically activated by P450 peroxidase activity to form cytotoxic quinoid species.
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PMID:Catechin metabolism: glutathione conjugate formation catalyzed by tyrosinase, peroxidase, and cytochrome p450. 1145 30

Catechol estrogens and catecholamines are metabolized to quinones, and the metabolite catechol (1,2-dihydroxybenzene) of the leukemogenic benzene can also be oxidized to its quinone. We report here that quinones obtained by enzymatic oxidation of catechol and dopamine with horseradish peroxidase, tyrosinase or phenobarbital-induced rat liver microsomes react with DNA by 1,4-Michael addition to form predominantly depurinating adducts at the N-7 of guanine and the N-3 of adenine. These adducts are analogous to the ones formed with DNA by enzymatically oxidized 4-catechol estrogens (Cavalieri,E.L., et al. (1997) PROC: Natl Acad. Sci., 94, 10937). The adducts were identified by comparison with standard adducts synthesized by reaction of catechol quinone or dopamine quinone with deoxyguanosine or adenine. We hypothesize that mutations induced by apurinic sites, generated by the depurinating adducts, may initiate cancer by benzene and estrogens, and some neurodegenerative diseases (e.g. Parkinson's disease) by dopamine. These data suggest that there is a unifying molecular mechanism, namely, formation of specific depurinating DNA adducts at the N-7 of guanine and N-3 of adenine, that could initiate many cancers and neurodegenerative diseases.
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PMID:Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. 1208 31

Catechin oxidation by peach polyphenol oxidase was performed in a pH range of 3.5-8.0. At acidic pH, maximal spectral changes were observed at 390nm and at pH 7.5, at 430nm. Catechin oxidation was studied at pH 7.5 to avoid the formation of free radicals. The results obtained allowed us to propose a pathway for the enzymatic oxidation of catechin, according to which enzymatic oxidation produces the corresponding catechin-o-quinone, which suffers the nucleophilic attack of another catechin unit, leading to the formation of a dimer. This dimer is then oxidized by the enzymatically generated o-quinone. The progress curves obtained for catechin oxidation by PPO showed a lag period, whose length changed with enzyme and substrate concentrations, and which must have been caused by the chemical reactions taking place after the enzymatic reaction. The results obtained by simulation of the model produced the same qualitative dependences as obtained experimentally.
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PMID:Kinetic analysis of catechin oxidation by polyphenol oxidase at neutral pH. 1518 68

Hybrid density functional theory with the B3LYP functional has been used to investigate the catalytic mechanism of catechol oxidase. Catechol oxidase belongs to a class of enzymes that has a copper dimer with histidine ligands at the active site. Another member of this class is tyrosinase, which has been studied by similar methods previously. An important advantage for the present study compared to the one for tyrosinase is that X-ray crystal structures exist for catechol oxidase. The most critical step in the mechanism for catechol oxidase is where the peroxide O-O bond is cleaved. In the suggested mechanism this cleavage occurs in concert with a proton transfer from the substrate. Shortly after the transition state is passed there is another proton transfer from the substrate, which completes the formation of a water molecule. An important feature of the mechanism, like the one for tyrosinase, is that no proton transfers to or from residues outside the metal complex are needed. The calculated energetics is in reasonable agreement with experiments. Comparisons are made to other similar enzymes studied previously.
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PMID:The catalytic cycle of catechol oxidase. 1518 33

Protector-II (Pr-II) of the Japanese morning glory (Pharbitis nil Choisy) was inactivated by exposure to polyphenol oxidase. An unidentified protector in the same molecular weight range obtained from sunflower was also inactivated by this enzyme. Earlier speculations that protectors might be lipoprotein in nature were negated by the fact that neither lipase nor protease inactivated the protectors. The protectors were also not inactivated by incubating with alpha-amylase, DNase, or RNase. Catechol mimics Pr and is inactivated by polyphenol oxidase. The oxidation of catechol to o-quinone is accompanied by a loss of chromophores that absorb ultraviolet light and the appearance of a reddish brown color. Similarly, when the relatively low molecular weight auxin protectors (Pr-II class) were incubated with polyphenol oxidase, their oxidation was also frequently associated with the formation of brown color, and oxidation with H(2)O(2) caused a loss of ultraviolet-absorbing chromophores. The data indicate that auxin protectors contain o-dihydroxyphenolic groups at their active site.That o-dihydroxyphenols inhibit indoleacetic acid oxidation has been demonstrated by numerous workers. It is suggested that the high molecular weight auxin protectors and the phenolic compounds described by other authors comprise part of a metabolic system concerned with the regulation of peroxidase-catalyzed redox reactions.
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PMID:Studies on Auxin Protectors: IX. Inactivation of Certain Protectors by Polyphenol Oxidase. 1665 85

The ability of copper proteins to process dioxygen at ambient conditions has inspired numerous research groups to study their structural, spectroscopic and catalytic properties. Catechol oxidase is a type-3 copper enzyme usually encountered in plant tissues and in some insects and crustaceans. It catalyzes the conversion of a large number of catechols into the respective o-benzoquinones, which subsequently auto-polymerize, resulting in the formation of melanin, a dark pigment thought to protect a damaged tissue from pathogens. After the report of the X-ray crystal structure of catechol oxidase a few years earlier, a large number of publications devoted to the biomimetic modeling of its active site appeared in the literature. This critical review (citing 114 references) extensively discusses the synthetic models of this enzyme, with a particular emphasis on the different approaches used in the literature to study the mechanism of the catalytic oxidation of the substrate (catechol) by these compounds. These are the studies on the substrate binding to the model complexes, the structure-activity relationship, the kinetic studies of the catalytic oxidation of the substrate and finally the substrate interaction with (per)oxo-dicopper adducts. The general overview of the recognized types of copper proteins and the detailed description of the crystal structure of catechol oxidase, as well as the proposed mechanisms of the enzymatic cycle are also presented.
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PMID:Synthetic models of the active site of catechol oxidase: mechanistic studies. 1693 29

An electrochemical biosensor using tyrosinase was constructed for the determination of catechol. The enzyme was extracted from a plant source Amorphophallus companulatus and entrapped in agarose-guar gum composite biopolymer matrix. Catechol was determined by direct reduction of biocatalytically liberated quinone species at -0.1 V versus Ag/AgCl (3M KCl). The response was found to be linear and concentration dependent in the range of 6 x 10(-5) to 8 x 10(-4)M with a lower detection limit of 6 microM. It has reusability up to 20 cycles and a shelf life of more than 2 months when stored at 4 degrees C.
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PMID:Electrochemical biosensor for catechol using agarose-guar gum entrapped tyrosinase. 1711 74

A novel bifunctional catalase with an additional phenol oxidase activity was isolated from a thermophilic fungus, Scytalidium thermophilum. This extracellular enzyme was purified ca. 10-fold with 46% yield and was biochemically characterized. The enzyme contains heme and has a molecular weight of 320 kDa with four 80 kDa subunits and an isoelectric point of 5.0. Catalase and phenol oxidase activities were most stable at pH 7.0. The activation energies of catalase and phenol oxidase activities of the enzyme were found to be 2.7 +/- 0.2 and 10.1 +/- 0.4 kcal/mol, respectively. The pure enzyme can oxidize o-diphenols such as catechol, caffeic acid, and L-DOPA in the absence of hydrogen peroxide and the highest oxidase activity is observed against catechol. No activity is detected against tyrosine and common laccase substrates such as ABTS and syringaldazine with the exception of weak activity with p-hydroquinone. Common catechol oxidase inhibitors, salicylhydroxamic acid and p-coumaric acid, inhibit the oxidase activity. Catechol oxidation activity was also detected in three other catalases tested, from Aspergillus niger, human erythrocyte, and bovine liver, suggesting that this dual catalase-phenol oxidase activity may be a common feature of catalases.
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PMID:Purification, characterization, and identification of a novel bifunctional catalase-phenol oxidase from Scytalidium thermophilum. 1836 15


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