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)

When the Legionnaires' disease (LD) bacterium is grown on supplemented Mueller-Hinton agar, brown pigmentation of the medium occurs. Since this browning may result from tyrosinase-mediated formation of melanin, we supplemented yeast-extract agar with various aromatic precursors of melanin and inoculated it with eight strains of the LD bacterium. Browning occurred with growth of each LD strain of the bacterium on yeast-extract agar enriched with 2.5 mmol/L of L-phenylalanine or L-tyrosine but not without such enrichment. Equimolar D-phenylalanine or D-tryosine in yeast-extract agar did not enhance browning. The LD bacterium may possess L-phenylalanine hydroxylase activity, but it does not use D-aromatic amino acids effectively in pigment production.
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PMID:Aromatic substrate specificity of browning by cultures of the Legionnaires' disease bacterium. 10 39

From initial velocity studies a sequential mechanism for the reactions catalysed by phenoloxidase from potatoes is indicated. The data are in accordance with an ordered addition of oxygen and phenolic substrate to the enzyme, with oxygen being the first substrate bound at thermodynamic equilibrium. The Michaelis constants for L-tyrosine, L-dopa, and chlorogenic acid are 1.4 X 10(-3), 3.3 X 10(-4), and 1.4 X 10(-4) mol/l, respectively. The dissociation constant for the enzyme-oxygen complex is about 10(-3) mol/l. In the presence of chlorogenic acid no lag phase occurs in the course of L-tyrosine oxidation. With increasing amounts of chlorogenic acid the tyrosinase activity goes through a maximum. The significance of these findings for the in vivo action of the enzyme is discussed.
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PMID:Studies on enzymic browning of potatoes (Solanum tuberosum). III. Kinetics of potato phenoloxidase (EC 1.14.18.1 monophenol, dihydroxyphenylalanine: oxygen-oxidoreductase). 40 77

The melanogenic activity of tyrosinase as a function of temperature was studied in 9 different skin and melanoma tissues of vertebrates. The 600 times g supernatant fraction of tissue homogenates was incubated with 14C-L-tyrosine at 0 degrees to 60 degrees C for 16 hr and the 14C-melanin product was determined. The range of optimal temperature occurred at 35 degrees to 45 degrees C. The maximal activity and thermostability depended on the source of the enzyme preparation utilized. Thermal activation and species differences in the optimal temperature for maximal activity are complicated processes which depend upon many factors. At cold conditions, a higher percentage of maximal activity was achieved with enzyme from cold-blooded species than with enzyme from warm-blooded species.
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PMID:Thermal activation and inactivation of melanin formation in vertebrate skins and melanomas. 80 28

Pigmentation of RVH 421 human melanoma cells is induced when cell division is inhibited by cytochalasin D or L-tyrosine phosphate. Increased pigmentation correlates with increased tyrosinase activity when this is monitored over a time-course. Parallel measurements show that the amount of tyrosinase mRNA correlates with enzyme activity in cells growing without these additives. In contrast, in the presence of cytochalasin D or L-tyrosine phosphate, the increase in amount of tyrosinase mRNA is not sufficient to account for the increase in enzyme activity, indicating that these compounds act mainly at a post-transcriptional level.
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PMID:Induction of tyrosinase in human melanoma cells by L-tyrosine phosphate and cytochalasin D. 137 60

Human tyrosinase (5.5 mg) has been purified from a single human melanotic melanoma metastasis (50.5 g). In the presence of dioxygen, L-tyrosine proved to be a very poor substrate for this enzyme with barely detectable activity compared to L-dopa. However, saturating superoxide anion (i.e., greater than 5 x 10(-3) M) enhanced the oxidation rate of L-tyrosine to dopachrome 40-fold. Hydrogen peroxide was shown to be a competitive inhibitor of tyrosinase when L-tyrosine was the substrate. This reversible inhibition is based on a slow pseudocatalase activity for tyrosinase. Monothiols and dithiols inhibit tyrosinase by different mechanisms. Reduced human thioredoxin and 2,3-dithiopropanol are allosteric inhibitors of tyrosinase yielding bis-cysteinate complexes with one of the copper atoms in the enzyme active site. Bis-cysteinate tyrosinase activity is down-regulated to 30% of native enzyme activity in the L-dopa assay; suggesting a true regulatory role for dithiols. Monothiols such as reduced glutathione and beta-mercaptoethanol are much less reactive with tyrosinase although 10(-3) M monothiol totally inhibits enzyme activity. Reduced thioredoxin inhibits tyrosinase 23-fold more than reduced glutathione under the same experimental conditions.
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PMID:Studies on the reactions between human tyrosinase, superoxide anion, hydrogen peroxide and thiols. 165 10

Variants of the Bomirski family of hamster melanomas whose proliferative rates differ inversely with the genetically determined degree of melanogenesis were probed for two proteins critical in melanogenesis: tyrosinase and catalase-B (gp 75). The parental black tumor Ma contained both proteins in abundance. The amelanotic variant Ab, inducible in culture with L-tyrosine or L-dopa to form melanosomes and to melanize, had minimal tyrosinase, despite high levels of (tyr)mRNA, and no gp 75. Variant MI, hypomelanotic despite abundant tyrosinase, and synthesizing predominantingly pheo-(red) melanin, expressed barely detectable gp 75. These findings suggest a regulatory control of melanogenesis distal to (tyr)mRNA and strengthen the hypothesis that in vivo tyrosinase without catalase-B favors pheo- over eumelanogenesis.
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PMID:Molecular mechanisms governing melanogenesis in hamster melanomas: relative abundance of tyrosinase and catalase-B (gp 75). 167 30

The kinetic behavior of the melanin biosynthesis pathway from L-tyrosine up to dopachrome has been studied from experimental and simulation assays. The reaction mechanism proposed is based on a single active site of tyrosinase. The diphenolase and monophenolase activities of tyrosinase involve one single (oxidase) and two overlapped (hydroxylase and oxidase) catalytic cycles, respectively. The stoichiometry of the pathway implies that one molecule of tyrosinase must accomplish two turnovers in the hydroxylase cycle for each one in the oxidase cycle. Furthermore, the steady-state rates of dopachrome production and O2 consumption from tyrosine and L-dopa, also fulfill the stoichiometry of the pathway: VO2T/VDCT = 1.5 and VO2T/VDCD = 1.0, where T represents L-tyrosine, DC represents dopachrome, and D represents L-dopa. It has been ascertained by high performance liquid chromatography that in the steady-state, a quantity of dopa is accumulated ([D]ss) which fulfills the constant ratio [D]ss = R[T]0. Taking this ratio into account, an analytical expression has been deduced for the monophenolase activity of tyrosinase. In this expression kcatT congruent to (2/3)k3(K1/K2)R, revealing that kcatT is not a true catalytic constant, since it also depends on equilibrium constants and on the experimental R = 0.057. This low value explains the lower catalytic efficiency of tyrosinase on tyrosine than on dopa, (VmaxT/KmT)/(VmaxD/KmD) congruent to (2/3)R, since a significant portion of tyrosinase is scavenged from the catalytic turnover as dead-end complex EmetT in the steady-state of the monophenolase activity of tyrosinase.
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PMID:Analysis of a kinetic model for melanin biosynthesis pathway. 174 Apr 28

As a part of an ongoing project aimed at developing new skin depigmenting agents, the ability of variously substituted 2-aryl-1,3-thiazolidines to inhibit melanogenesis in vitro was investigated. At 0.2 mM concentration 2-(2'-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid (Th2), as well as the descarboxy analog (Th1) and, to a lower extent, the 4'-hydroxy isomer (Th3) all proved capable of preventing the tyrosinase catalyzed conversion of 0.2 mM L-tyrosine to melanin. Spectrophotometric monitoring of the reaction course in the presence of Th2 showed the initial formation of a yellow chromophore (lambda max 400 nm) which slowly decayed, being eventually replaced by a new absorption maximum centered at 305 nm. HPLC analysis of the final incubation mixture revealed the presence of a major product (lambda max 306 nm), ninhydrin and ferric chloride positive, which was isolated by gel filtration on Sephadex G-10 and was identified as beta-[7-(3-carboxy-5-hydroxy-3,4-dihydro-2H-1,4-benzothiazinyl)]al anine (DBA) by 1H-NMR spectroscopy. Attempts to isolate the intermediate with lambda max 400 nm were hampered by its marked instability under the usual chromatographic conditions. However, the nature of the chromophore, coupled with mechanistic considerations, suggested for the compound the Schiff base-containing structure 3,4-dihydroxy-5-S-(N-salicylidenecysteinyl)phenylalanine (salcysdopa). This was substantiated by: (i) the formation of a zinc complex (lambda max 349 nm) analogous to that observed with the model Schiff base N-salicylidene leucine; and (ii) detection by 1H-NMR of a Schiff base resonance at delta 8.1 during the yellow chromophoric phase of the reaction. It was concluded that 1,3-thiazolidines inhibit melanin formation by a mechanism that involves the trapping of enzymically generated dopaquinone by the -SH containing Schiff base arising by cleavage of the thiazolidine ring. The salcysdopa adduct thus formed undergoes hydrolysis and subsequent ring closure to give eventually the colorless DBA.
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PMID:2-Aryl-1,3-thiazolidines as masked sulfhydryl agents for inhibition of melanogenesis. 190 Dec 20

Exposure of hamster amelanotic melanoma cells to L-tyrosine caused a time-dependent increase of tyrosinase protein concentrations, tyrosinase activity and level of cell pigmentation. In contrast, Northern blot analysis using mouse tyrosinase cDNA showed a steady level of tyrosinase mRNA. Thus in hamster melanoma cells the stimulation of intracellular tyrosinase concentration by L-tyrosine is mediated mainly via a posttranscriptional mechanism.
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PMID:L-tyrosine induces tyrosinase expression via a posttranscriptional mechanism. 190 10

Melanin biosynthesis is a multistep process with the first step being the conversion of L-tyrosine to L-Dopa catalyzed by the enzyme tyrosinase. The enzymes which catalyze the other steps of melanogenesis are not known. One murine pigmentation gene, the brown (b) locus, when mutated, leads to a brown or hypopigmented coat. The b-locus protein has been shown to display catalase activity. The human b-locus, therefore, is designated as CAS2. We used the mouse b-locus cDNA to isolate the human homologue, which in turn, was used to map the CAS2 locus to a human chromosome. The potential CAS2 protein codes for 527 amino acids containing a putative signal sequence and transmembrane domain. The CAS2 protein has primary and probably secondary structures similar to human tyrosinase. The CAS2 was mapped to human Chromosome 9 by somatic cell hybridization and, more specifically, to 9p22-pter by in situ hybridization. The assignment of CAS2 on the human Chromosome 9 extends this region of known homology on mouse Chromosome 4.
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PMID:Mapping the human CAS2 gene, the homologue of the mouse brown (b) locus, to human chromosome 9p22-pter. 190 72


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