Tyrosinase

Tyrosinase is an is_associated_with::oxidase that is the rate-limiting is_associated_with::enzyme for controlling the production of is_associated_with::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 is_associated_with::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 is_associated_with::potato exposed to air. It is found inside is_associated_with::melanosomes which are synthesised in the skin is_associated_with::melanocytes. In humans, the tyrosinase enzyme is encoded by the TYR is_associated_with::gene.

Clinical significance
A mutation in the tyrosinase gene resulting in impaired tyrosinase production leads to type I oculocutaneous is_associated_with::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 is_associated_with::hyperpigmentation of the skin, such as is_associated_with::melasma and age spots.

Several polyphenols, including is_associated_with::flavonoids or is_associated_with::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.

Significance in food industry
In food industry, tyrosinase inhibition is desired a tyrosinase catalyzes the oxidation of is_associated_with::phenolic compounds found in fruits and vegetables into is_associated_with::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 is_associated_with::kojic acid, is_associated_with::tropolone, is_associated_with::coumarins, is_associated_with::vanillic acid, is_associated_with::vanillin, and is_associated_with::vanillic alcohol.

Significance in insects
Tyrosinase has a wide range of functions in insects, including wound healing, is_associated_with::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.

Catalyzed reaction
Tyrosinase carries out the oxidation of phenols such as is_associated_with::tyrosine and is_associated_with::dopamine using dioxygen (O2). In the presence of is_associated_with::catechol, is_associated_with::benzoquinone is formed (see reaction below). Hydrogens removed from catechol combine with is_associated_with::oxygen to form is_associated_with::water.

The substrate specificity becomes dramatically restricted in mammalian tyrosinase which uses only L-form of tyrosine or DOPA as substrates, and has restricted requirement for L-DOPA as cofactor.

Structure
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 is_associated_with::primary structure, size, glycosylation pattern, and activation characteristics. However, all tyrosinases have in common a binuclear, type 3 copper centre within their is_associated_with::active sites. Here, two copper atoms are each coordinated with three is_associated_with::histidine residues.

Human tyrosinase
Human tyrosinase is a single membrane-spanning is_associated_with::transmembrane protein. In humans, tyrosinase is sorted into is_associated_with::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 is_associated_with::melanocyte.

As opposed to fungal tyrosinase, human tyrosinase is a membrane-bound is_associated_with::glycoprotein and has 13% carbohydrate content.

Active site


The two copper atoms within the active site of tyrosinase enzymes interact with is_associated_with::dioxygen to form a highly reactive chemical intermediate that then oxidizes the substrate. The activity of tyrosinase is similar to is_associated_with::catechol oxidase, a related class of copper is_associated_with::oxidase. Tyrosinases and is_associated_with::catechol oxidases are collectively termed is_associated_with::polyphenol oxidases.

Gene regulation
The gene for tyrosinase is regulated by the is_associated_with::microphthalmia-associated transcription factor (MITF).