Tyrosinase is an oxidase that is the rate-limitingenzyme for controlling the production of melanin. It is mainly involved in two distinct reactions of melanin synthesis; firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled or sliced potato exposed to air. It is found inside melanosomes which are synthesised in the skin melanocytes. In humans, the tyrosinase enzyme is encoded by the TYRgene.
A mutation in the tyrosinase gene resulting in impaired tyrosinase production leads to type I oculocutaneous albinism, a hereditary disorder that affects one in every 17,000 people.
Tyrosinase activity is very important. If uncontrolled during melanoma, it results in increased melanin synthesis. Decreasing tyrosinase activity has been targeted for the betterment or prevention of conditions related to the hyperpigmentation of the skin, such as melasma and age spots.
Several polyphenols, including flavonoids or stilbenoid, substrate analogues, free radical scavengers, and copper chelators, have been known to inhibit tyrosinase. Henceforth, the medical and cosmetic industries are focusing research on tyrosinase inhibitors to treat skin disorders.
In food industry, tyrosinase inhibition is desired a tyrosinase catalyzes the oxidation of phenolic compounds found in fruits and vegetables into quinones, which gives an undesirable taste and color and also decreases the availability of certain essential amino acids as well as the digestibility of the products. As such, highly effective tyrosinase inhibitors are also needed in agriculture and the food industry. Well known tyrosinase inhibitors include kojic acid,tropolone,coumarins,vanillic acid, vanillin, and vanillic alcohol.
Tyrosinase has a wide range of functions in insects, including wound healing, sclerotization, melanin synthesis and parasite encapsulation. As a result, it is an important enzyme is the defensive mechanisms of insects and some insecticides are aimed to inhibit tyrosinase.
Tyrosinases have been isolated and studied from a wide variety of plant, animal, and fungal species. Tyrosinases from different species are diverse in terms of their structural properties, tissue distribution, and cellular location. No common tyrosinase protein structure occurring across all species has been found. The enzymes found in plant, animal, and fungal tissue frequently differ with respect to their primary structure, size, glycosylation pattern, and activation characteristics. However, all tyrosinases have in common a binuclear, type 3 copper centre within their active sites. Here, two copper atoms are each coordinated with three histidineresidues.
Human tyrosinase is a single membrane-spanning transmembrane protein. In humans, tyrosinase is sorted into melanosomes and the catalytically active domain of the protein resides within melanosomes. Only a small, enzymatically inessential part of the protein extends into the cytoplasm of the melanocyte.
As opposed to fungal tyrosinase, human tyrosinase is a membrane-bound glycoprotein and has 13% carbohydrate content.
Crystallographic structure of a Streptomyces-derived tyrosinase in complex with a so-called "caddie protein" In all models, only the tyrosinase molecule is shown, copper atoms are shown in green and the molecular surface is shown in red. In models D and E, histidine amino acids are shown as a blue line representation. From model E, each copper atom within the active site is indeed complexed with three histidine residues, forming a type 3 copper center. From models C and D, the active site for this protein can be seen to sit within a pillus formed on the molecular surface of the molecule.
^Barton DE, Kwon BS, Francke U (Jul 1988). "Human tyrosinase gene, mapped to chromosome 11 (q14----q21), defines second region of homology with mouse chromosome 7". Genomics3 (1): 17–24. doi:10.1016/0888-7543(88)90153-X. PMID3146546.
^Witkop CJ (Oct 1979). "Albinism: hematologic-storage disease, susceptibility to skin cancer, and optic neuronal defects shared in all types of oculocutaneous and ocular albinism". The Alabama Journal of Medical Sciences16 (4): 327–30. PMID546241.
^Mendes E, Perry Mde J, Francisco AP (May 2014). "Design and discovery of mushroom tyrosinase inhibitors and their therapeutic applications". Expert Opinion on Drug Discovery9 (5): 533–54. doi:10.1517/17460441.2014.907789. PMID24708040.
^Rescigno A, Sollai F, Pisu B, Rinaldi A, Sanjust E (Aug 2002). "Tyrosinase inhibition: general and applied aspects". Journal of Enzyme Inhibition and Medicinal Chemistry17 (4): 207–18. doi:10.1080/14756360210000010923. PMID12530473.
^Sollai, Francesca; Zucca, Paolo; Sanjust, Enrico; Steri, Daniela; Rescigno, Antonio (2008). "Umbelliferone and Esculetin: Inhibitors or Substrates for Polyphenol Oxidases?". Biological & Pharmaceutical Bulletin31 (12): 2187–2193. doi:10.1248/bpb.31.2187.
^Rescigno A, Casañola-Martin GM, Sanjust E, Zucca P, Marrero-Ponce Y (Mar 2011). "Vanilloid derivatives as tyrosinase inhibitors driven by virtual screening-based QSAR models". Drug Testing and Analysis3 (3): 176–81. doi:10.1002/dta.187. PMID21125547.
^Hearing VJ, Ekel TM, Montague PM, Nicholson JM (Feb 1980). "Mammalin tyrosinase. Stoichiometry and measurement of reaction products". Biochimica Et Biophysica Acta611 (2): 251–68. doi:10.1016/0005-2744(80)90061-3. PMID6766744.
^PDB: 1WX3; Matoba Y, Kumagai T, Yamamoto A, Yoshitsu H, Sugiyama M (2006). "Crystallographic evidence that the dinuclear copper center of tyrosinase is flexible during catalysis". J. Biol. Chem.281 (13): 8981–8990. doi:10.1074/jbc.M509785200. PMID16436386.
^Hou L, Panthier JJ, Arnheiter H (Dec 2000). "Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF". Development127 (24): 5379–89. PMID11076759.
^Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID19067971.