The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

2001 ◽  
Vol 354 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Concepción OLIVARES ◽  
Celia JIMÉNEZ-CERVANTES ◽  
José Antonio LOZANO ◽  
Francisco SOLANO ◽  
José Carlos GARCÍA-BORRÓN
Keyword(s):  
Carboxylic Acid ◽  
Substrate Specificity ◽  
Transient Expression ◽  
Oxidase Activity ◽  
Melanin Synthesis ◽  
Catalytic Activities ◽  
Human Melanocytes ◽  
Related Proteins ◽  
Rate Limiting ◽  
Human Tyrosinase

Melanin synthesis in mammals is catalysed by at least three enzymic proteins, tyrosinase (monophenol dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and tyrosinase-related proteins (tyrps) 1 and 2, whose genes map to the albino, brown and slaty loci in mice, respectively. Tyrosinase catalyses the rate-limiting generation of l-dopaquinone from l-tyrosine and is also able to oxidize l-dopa to l-dopaquinone. Conversely, mouse tyrp1, but not tyrosinase, catalyses the oxidation of the indolic intermediate 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into the corresponding 5,6-indolequinone-2-carboxylic acid, thus promoting the incorporation of DHICA units into eumelanin. The catalytic activities of the human melanogenic enzymes are still debated. TYRP1has been reported to lack DHICA oxidase activity, whereas tyrosinase appears to accelerate DHICA consumption, thus raising the question of DHICA metabolism in human melanocytes. Here we have used two different approaches, comparison of the catalytic activities of human melanocytic cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, and transient expression of TYR and tyr genes in COS7 cells, to demonstrate that human tyrosinase actually functions as a DHICA oxidase, as opposed to the mouse enzyme. Therefore, human tyrosinase displays a broader substrate specificity than its mouse counterpart, and might be at least partially responsible for the incorporation of DHICA units into human eumelanins.

scholarly journals The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase

2001 ◽  
Vol 354 (1) ◽  
pp. 131 ◽  
Author(s):  
Concepción OLIVARES ◽  
Celia JIMÉNEZ-CERVANTES ◽  
José Antonio LOZANO ◽  
Francisco SOLANO ◽  
José Carlos GARCÍA-BORRÓN
Keyword(s):  
Carboxylic Acid ◽  
Oxidase Activity ◽  
Human Tyrosinase

Are Human Tyrosinase and Related Proteins Suitable Targets for Melanoma Therapy?

2016 ◽  
Vol 16 (27) ◽  
pp. 3033-3047 ◽  
Author(s):  
Elina Buitrago ◽  
Renaud Hardré ◽  
Romain Haudecoeur ◽  
Hélène Jamet ◽  
Catherine Belle ◽  
...  
Keyword(s):  
Related Proteins ◽  
Human Tyrosinase ◽  
Melanoma Therapy

scholarly journals Tyrosinase Nanoparticles: Understanding the Melanogenesis Pathway by Isolating the Products of Tyrosinase Enzymatic Reaction

2021 ◽  
Vol 22 (2) ◽  
pp. 734
Author(s):  
Paul K. Varghese ◽  
Mones Abu-Asab ◽  
Emilios K. Dimitriadis ◽  
Monika B. Dolinska ◽  
George P. Morcos ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Large Scale ◽  
Magnetic Beads ◽  
Enzymatic Reaction ◽  
Oculocutaneous Albinism ◽  
Transmission Electron ◽  
Hill Kinetics ◽  
Rate Limiting ◽  
Human Tyrosinase

Human Tyrosinase (Tyr) is the rate-limiting enzyme of the melanogenesis pathway. Tyr catalyzes the oxidation of the substrate L-DOPA into dopachrome and melanin. Currently, the characterization of dopachrome-related products is difficult due to the absence of a simple way to partition dopachrome from protein fraction. Here, we immobilize catalytically pure recombinant human Tyr domain (residues 19–469) containing 6xHis tag to Ni-loaded magnetic beads (MB). Transmission electron microscopy revealed Tyr-MB were within limits of 168.2 ± 24.4 nm while the dark-brown melanin images showed single and polymerized melanin with a diameter of 121.4 ± 18.1 nm. Using Hill kinetics, we show that Tyr-MB has a catalytic activity similar to that of intact Tyr. The diphenol oxidase reactions of L-DOPA show an increase of dopachrome formation with the number of MB and with temperature. At 50 °C, Tyr-MB shows some residual catalytic activity suggesting that the immobilized Tyr has increased protein stability. In contrast, under 37 °C, the dopachrome product, which is isolated from Tyr-MB particles, shows that dopachrome has an orange-brown color that is different from the color of the mixture of L-DOPA, Tyr, and dopachrome. In the future, Tyr-MB could be used for large-scale productions of dopachrome and melanin-related products and finding a treatment for oculocutaneous albinism-inherited diseases.

scholarly journals Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

2021 ◽  
Vol 22 (7) ◽  
pp. 3755
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  
Keyword(s):  
Uv Radiation ◽  
Therapeutic Potential ◽  
Melanin Synthesis ◽  
Uvb Radiation ◽  
Biochemical Basis ◽  
Skin Hyperpigmentation ◽  
Human Melanocytes ◽  
Anti Cancer ◽  
Normal Human

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

scholarly journals Substrate specificity of sheep liver sorbitol dehydrogenase

1998 ◽  
Vol 330 (1) ◽  
pp. 479-487 ◽  
Author(s):  
I. Rune LINDSTAD ◽  
Peter KÖLL ◽  
John S. McKINLEY-McKEE
Keyword(s):  
Substrate Specificity ◽  
Ternary Complex ◽  
Kinetic Mechanism ◽  
Sorbitol Dehydrogenase ◽  
Hydroxyl Group ◽  
Enzyme Active Site ◽  
Sheep Liver ◽  
Rate Limiting Step ◽  
Steady State Kinetics ◽  
Rate Limiting

The substrate specificity of sheep liver sorbitol dehydrogenase has been studied by steady-state kinetics over the range pH 7-10. Sorbitol dehydrogenase stereo-selectively catalyses the reversible NAD-linked oxidation of various polyols and other secondary alcohols into their corresponding ketones. The kinetic constants are given for various novel polyol substrates, including L-glucitol, L-mannitol, L-altritol, D-altritol, D-iditol and eight heptitols, as well as for many aliphatic and aromatic alcohols. The maximum velocities (kcat) and the substrate specificity-constants (kcat/Km) are positively correlated with increasing pH. The enzyme-catalysed reactions occur by a compulsory ordered kinetic mechanism with the coenzyme as the first, or leading, substrate. With many substrates, the rate-limiting step for the overall reaction is the enzyme-NADH product dissociation. However, with several substrates there is a transition to a mechanism with partial rate-limitation at the ternary complex level, especially at low pH. The kinetic data enable the elucidation of new empirical rules for the substrate specificity of sorbitol dehydrogenase. The specificity-constants for polyol oxidation vary as a function of substrate configuration with D-xylo > d-ribo > L-xylo > d-lyxo ≈ l-arabino > D-arabino > l-lyxo. Catalytic activity with a polyol or an aromatic substrate and various 1-deoxy derivatives thereof varies with -CH2OH >-CH2NH2 >-CH2OCH3 ≈-CH3. The presence of a hydroxyl group at each of the remaining chiral centres of a polyol, apart from the reactive C2, is also nonessential for productive ternary complex formation and catalysis. A predominantly nonpolar enzymic epitope appears to constitute an important structural determinant for the substrate specificity of sorbitol dehydrogenase. The existence of two distinct substrate binding regions in the enzyme active site, along with that of the catalytic zinc, is suggested to account for the lack of stereospecificity at C2 in some polyols.

Placental extracts regulate melanin synthesis in normal human melanocytes with alterations of mitochondrial respiration

2019 ◽  
Vol 28 ◽  
pp. 50-54 ◽  
Author(s):  
Satoshi Yoshimoto ◽  
Yoshiaki Ohagi ◽  
Moemi Yoshida ◽  
Hiroki Yanagi ◽  
Sawako Hibino ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Melanin Synthesis ◽  
Human Melanocytes ◽  
Normal Human

Harvest maturity related changes in the cold-induced activation of 1-aminocyclopropane-1-carboxylic acid metabolism in Granny Smith apples / Efecto del estado de madurez sobre la activación por frío del metabolismo del ácido 1-aminociclopropano-1-carboxílico en manzanas Granny Smith

1999 ◽  
Vol 5 (3) ◽  
pp. 223-228 ◽  
Author(s):  
C. Larrigaudiere ◽  
I. Recasens ◽  
J. Graell ◽  
M. Vendrell
Keyword(s):  
Carboxylic Acid ◽  
Ethylene Production ◽  
Oxidase Activity ◽  
Acid Metabolism ◽  
Cold Treatment ◽  
Acc Oxidase ◽  
Malus Domestica Borkh ◽  
Harvest Dates ◽  
Harmonization Process ◽  
Harvest Maturity

Changes in 1-aminocyclopropane-1-carboxylic acid metabolism in apples ( Malus domestica Borkh cv Granny Smith) were studied in relation to cold storage. Emphasis was given to the differential re sponsiveness of fruits to cold treatment as a function of stage of maturity at harvest. Fruits were held at 1 or 20 °C for 30 days, respectively, or exposed to 1 °C for 10 days and then storaged at 20 °C for up to 30 days. Fruits at 20 °C showed typical climacteric behavior. Differences at 1 °C between maturity stages in ethylene production and ACC oxidase activity were abolished, which showed that cold treatment is an important inducer of climacteric rise in preclimacteric Granny Smith apples. At 1 °C, ethylene production was lower than at 20 °C and the maxima in production were similar for all the stages of maturity, but took place at different times which corresponded exactly to the initial differ ences in harvest dates. After the transfer to 20 °C, fruits exhibited similar behavior as regards ethyl ene production, ACC oxidase activity, and ACC and MACC levels in relation to a harmonization process which is discussed in this study.

scholarly journals Frontispiece: Structure and Function of Human Tyrosinase and Tyrosinase-Related Proteins

2018 ◽  
Vol 24 (1) ◽  
Author(s):  
Xuelei Lai ◽  
Harry J. Wichers ◽  
Montserrat Soler-Lopez ◽  
Bauke W. Dijkstra
Keyword(s):  
Structure And Function ◽  
And Function ◽  
Related Proteins ◽  
Human Tyrosinase
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