Tyrosinase is an oxidase that is the rate-limiting enzyme 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 TYR gene.
Significance = Clinical significance =
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.
= Significance in food industry = In food industry, tyrosinase inhibition
is desired as 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.
= Significance in insects = 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. Catalyzed reaction
Tyrosinase carries out the oxidation of phenols such as tyrosine and dopamine
using dioxygen. In the presence of catechol, benzoquinone is formed.
Hydrogens removed from catechol combine with oxygen to form 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
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
histidine residues. = Human tyrosinase =
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.
= Active site = The two copper atoms within the active
site of tyrosinase enzymes interact with dioxygen to form a highly reactive
chemical intermediate that then oxidizes the substrate. The activity of
tyrosinase is similar to catechol oxidase, a related class of copper
oxidase. Tyrosinases and catechol oxidases are collectively termed
polyphenol oxidases. Gene regulation
The gene for tyrosinase is regulated by the microphthalmia-associated
transcription factor. References
External links GeneReviewsNIH/UW entry on
Oculocutaneous Albinism Type 1 Tyrosinase at the US National Library of
Medicine Medical Subject Headings