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)

We report the ability of 3-amino-L-tyrosine to act as a fully reversible competitive inhibitor of mushroom tyrosinase. The inhibition is linked to the ortho-aminophenol structure, and a copper bridging mechanism in the active site is proposed.
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PMID:Inhibition of mushroom tyrosinase by 3-amino-L-tyrosine: molecular probing of the active site of the enzyme. 314 Dec 7

We describe results demonstrating the positive regulation of melanogenesis by two substrates of the melanogenic pathway. We have found that L-tyrosine and L-dihydroxyphenylalanine (L-dopa), whose metabolic fates are affected by the activity of that pathway, can also act as its regulators. In living pigment cells, tyrosinase (EC 1.14.18.1), a crucial and rate-limiting enzyme of melanogenesis, acts in subcellular organelles known as melanosomes. Melanin is laid down only in these organelles. We demonstrate that supplementing Ham's F-10 medium with additional L-tyrosine or L-dopa during the culture of amelanotic Bomirski hamster melanoma cells results in a rapid increase in melanin formation, which is not simply due to greater availability of substrate. There is a rapid increase in tyrosinase activity and a large scale synthesis of melanosomes. The effects of L-tyrosine and L-dopa are prevented by the addition of cycloheximide. The actions of L-tyrosine and L-dopa are specific in that under similar conditions D-tyrosine, D-dopa, N-acetyl-L-tyrosine, L-phenylalanine, L-tryptophan and L-valine have little or no effect. The two substrates, L-tyrosine and L-dopa, appear to act through related but distinct mechanisms. Our findings provide an example of a little-known phenomenon: regulation of a differentiated eukaryotic phenotype through positive control by substrates in the pathway.
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PMID:Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa. 314 38

Dissociated pigmented epithelial (PE) cells from ciliary processes (CP) of bovine eyes were separated by isopycnic centrifugation in metrizamide gradients and further cultivated. The level of cellular contamination during separation of PE by non-pigmented epithelial (NPE) cells was estimated to be 5-10% and by non-epithelial cells (i.e. endothelial, fibroblasts and blood cells) less than 1%. Bovine PE cells were found to have different serum requirements than NPE to grow in vitro. PE cells were actively stimulated to proliferate in the presence of fetal calf serum for a few generations. Short-term culture of NPE was only obtained in media containing a low concentration of L-tyrosine and no serum. Two morphological markers, namely desmosomes and intermediate-sized filaments (IF) of the vimentin type, were found by immunolabeling to be coexpressed in cultured PE and were used as criteria to define the epithelial identity of these cells. The present study was unable to detect any tyrosinase activity in cultured PE cells.
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PMID:Separation of bovine pigmented ciliary epithelial cells by density gradient and further characterization in culture. 389 94

B-16 melanomas grown for 13 and 22 days after transplantation in mice were utilized in studies of subcellular distribution of tyrosinase activity and tyrosinase isozyme patterns. The tyrosinase activity utilizing L-tyrosine-14-C was higher in the younger than in the older melanomas. The percent of total activity distributed in the 144,000 g supernatant was 38% for the former and 46% for the latter. Both melanomas had higher percentage of activity confined in the pellet obtained by centrifuging the crude homogenate at 600 g. The digestion of P 600 g pellet by lipase liberated tyrosinase activity which was two fold of the activity originally counted in the pellet. Five isozymes wereobserved in the soluble tyrosinase and two in the solubilized tyrosinase.
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PMID:Tyrosinase activity and isozymes in B-16 mouse melanomas. 421 94

A simplified technique to detect polyphenol oxidase and melanin formation by Streptomyces culture filtrates was developed. The procedure involves the direct assay of pigment formation by the culture filtrate with 3-(3,4-dihydroxyphenyl)-L-alanine (L-dopa) as a substrate. Among cultures of the International Streptomyces Project, 34 failed to produce a diffusible dark brown pigment on peptone-yeast extract-iron-agar and synthetic tyrosine-agar and gave a negative reaction to the melanin formation test. Sixteen cultures produced a diffusible dark brown pigment on both peptone-yeast extract-iron-agar and synthetic tyrosine-agar and gave positive reactions to the test with either L-tyrosine or L-dopa as substrate. Twenty-one cultures produced a diffusible dark brown pigment on peptone-yeast extract-iron-agar, but failed to do so on synthetic tyrosine-agar. Most of these cultures gave a positive reaction to the test when L-dopa was used as the substrate. The correlation between chromogenicity on complex organic media and melanin formation was more clearly established with L-dopa as substrate than with synthetic tyrosine-agar in the present test. The melanin formation test by the present technique, instead of chromogenicity on complex organic media, is recommended as a key feature for the classification of Streptomyces.
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PMID:Chromogenicity of Streptomyces. 462 31

A particulate tyrosinase has been extracted and purified from tentacles of the sea anemone Metridium senile. The purified enzyme had properties in common with both mushroom and vertebrate tyrosinase and catalyzed three different reactions: oxidation of catechols, hydroxylation of L-tyrosine with L-dopa as cofactor and 5-hydroxylation of L-dopa. 5-Hydroxylation of L-dopa by an animal tyrosinase has not been reported earlier. The reaction could be analyzed under reducing conditions when the much faster oxidation of L-dopa to dopaquinone was inhibited. The conditions required for the accumulation of L-dopa and 5-hydroxydopa observed in vivo in tentacles of Metridium are discussed.
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PMID:Enzymatic 5-hydroxylation of L-dopa by a tyrosinase isolated from the sea anemone Metridium senile. 614 65

The medium of cultured melanoma cells was studied for tyrosine hydroxylation and dopa-oxidizing activity. The supernatant obtained after centrifugation at 100 000 g for 2 hours was treated with ammonium sulphate, and the precipitate obtained between 35 and 50% saturation was used. Dopa was determined as the product of tyrosine hydroxylation and 5-S-cysteinyldopa as the product of dopa oxidase activity. Determinations were performed with HPLC and electrochemical detection. Our preparation of culture medium of cells showed the following. 1) No hydroxylation of tyrosine in the absence of co-factor. 2) Hydroxylation of L-tyrosine in the presence of dopamine. No hydroxylation with boiled medium. Minimal effect of catalase on hydroxylation. 3) Hydroxylation of tyrosine in the presence of ascorbic acid. Hydroxylation was catalyzed also with boiled medium. Catalase strikingly diminished hydroxylation. 4) Oxidation of L-dopa to dopaquinone determined as its main reaction product with cysteine, 5-S-cysteinyl-dopa. There was negligible oxidation with boiled medium. 5) With dopamine as co-factor the catalysis of tyrosine hydroxylation was stereospecific for L-tyrosine. Dopa oxidase activity was also stereospecific for L-dopa.
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PMID:Tyrosinase activity in the medium of human melanoma cell cultures. 619 32

A tyrosinase purified from cultured human melanoma cells was studied for dopa oxidation and tyrosine oxygenation. Km for oxidation of L-dopa was 0.5 mM, and for D-dopa 3 mM. L-tyrosine was oxygenated only in the presence of a cosubstrate. L-Dopa was superior to D-dopa, dopamine, L- and D-alpha-methyldopa, dopac, and 5,6-dihydroxyindole-2-carboxylic acid as cosubstrate. Ascorbic acid, 5-S-cysteinyldopa, and 5-OH-dopa did not function as cosubstrates. The rate of tyrosine hydroxylation was much lower than that of dopa oxidation. Tyrosine inhibits dopa oxidation, and dopa in high concentrations inhibits tyrosine hydroxylation. The cosubstrate function of dopa, the substrate functions of dopa and tyrosine, and the mutual inhibition of tyrosinase by these compounds are explained in three equations.
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PMID:Dopa oxidation and tyrosine oxygenation by human melanoma tyrosinase. 619 34

To characterize how structural properties are related to the morphological differentiation of melanosomes, two forms of melanosomes, commonly seen in mammals, were isolated from B16 and Harding Passey (HP) mouse melanomas. From these morphologically different melanosomes, tyrosinase was solubilized by BRIJ-35 and purified by affinity chromatographies substituted with tyrosinase substrates. We found that tyrosine ethyl ester (TEE) and dopa are effective and specific in retaining tyrosinase as an affinity media and that enzyme retrieval with approximately 100% recovery is possible by a substrate, TEE, or a competitive inhibitor, N-acetyl L-tyrosine. The purified tyrosinase of B16 and HP melanosomes possessed a common antigenic site and revealed little difference in size and the Mikaelis constant for dopa utilization. It is likely that tyrosinase is involved in melanosome morphogenesis only through melanization, and that it is not directly related to the architecture, i.e., lamellar and granular patterns, of the inner matrix.
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PMID:Characterization of structural properties for morphological differentiation of melanosomes: I. Purification of tyrosinase by tyrosine affinity chromatography and its characterization in B16 and Harding Passey melanomas. 679 93

The hair follicles and the eyes of pallid mice (C57/6J-Pa/Pa) and those of black mice (C57/6J-+/Pa) were examined ultrastructurally, histochemically, and biochemically to determine the cause of pigment dilution. The pigment cells in the hair follicles and the eyes of pallid mice have less mature melanosomes than those of black mice. In the hair follicles the pallid melanosomes were transferred into keratinocytes and became aggregated. In the eyes they were already aggregated within the pigment cells and were digested in acid phosphatase-positive lysosomes. The activity of acid phosphatase, a marker of lysosomal enzymes was significantly higher in pallid hair follicles and eyes than in black hair follicles and eyes. Dopa reactions at light and electron microscopical level indicated that the pigment cells in each tissue produced a large amount of Dopa oxidase when compared with those in each black counterpart. However, the rate of hydroxylation of L-tyrosine-3,5-3H was significantly lower in the pallid eyes than in black eyes, while this rate was significantly higher in pallid hair follicles than in black hair follicles. Immediate digestion of melanosomes within the pigment cells, i.e., autophagocytosis, seemed to explain the low activity in the pallid eyes. The diluted coat and eye colors of pallid mice are, therefore, not related to low Dopa oxidase activity but to immaturity of melanosomes and high activities of lysosomal enzymes; these enzymes seem to digest many of these immature melanosomes and contribute to the diluted coat and eye colors of pallid mice.
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PMID:Ultrastructural, histochemical, and biochemical studies of the melanin metabolism in eye and skin of pallid mice. 680 5


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