Tyrosinase

As opposed to fungal tyrosinase, human tyrosinase is a membrane-bound glycoprotein and has 13% carbohydrate content.^[14]

The derived TYR allele (rs2733832) is associated with lighter skin pigmentation in human populations. It is most common in Europe, but is also found at lower, moderate frequencies in Central Asia, the Middle East, North Africa, and among the San and Mbuti Pygmies.^[15]

Bacterial

In peatlands, bacterial tyrosinases are proposed to act as key regulators of carbon storage by removing phenolic compounds, which inhibit the degradation of organic carbon.^[16]

Gene regulation

The gene for tyrosinase is regulated by the microphthalmia-associated transcription factor (MITF).^[17][18]

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 20,000 people.^[20]

Tyrosinase activity is very important. If uncontrolled during the

Several polyphenols, including flavonoids or stilbenoid, substrate analogues, free radical scavengers, and copper chelators, have been known to inhibit tyrosinase.^[22] Henceforth, the medical and cosmetic industries are focusing research on tyrosinase inhibitors to treat skin disorders.^[5]

Inhibitors

Known Tyrosinase inhibitors are the following:^[23]

• Azelaic acid
• 4-Butylresorcinol
• Hydroquinone
• L-ascorbic acid - Vitamin C
• Tranexamic acid

Genetics

While albinism is common, there have only been a few studies about the genetic mutations in the tyrosinase genes of animals. One of them was on Bubalus bubalis (water buffalo). The tyrosinase mRNA sequence of the wild-type B. bubalis is 1,958 base pairs (bp) with an open reading frame (ORF) of 1,593 bp long, which translates to 530 amino acids. Meanwhile, the tyrosinase gene of the albino B. bubalis (GenBank JN_887463) is truncated at position 477, caused by a point mutation in nucleotide 1431 which converts a Tryptophan (TGG) into a stop codon (TGA), resulting in a shorter and inactive tyrosinase gene.^[24] Other albinos have point mutations that appear to inactivate Tyrosinase without truncation (see table and figure for examples).

Knowing that there are a few studies about the genomic data of the tyrosinase gene, there are only a handful of studies on the mutations in albino amphibians. Miura et al. (2018) investigates the amino acid mutations in the tyrosinase gene in three albino frogs: Pelophylax nigromaculatus (pond frog), Glandirana rugosa (wrinkled frog) and Fejervarya kawamurai (rice frog). In total, five different populations were studied of which three were P. nigromaculatus and one each of G. rugosa and F. kawamurai. In two of the three P. nigromaculatus populations, there was a frameshift mutation because of the insertion of a thymine within exons 1 and 3, and the third population lacked three nucleotides that encoded a Lysine in exon 1. The population of G. rugosa had a missense mutation where there was an amino acid substitution from a Glycine to Aspartic acid, and the mutation of F. kawamurai was also an amino acid substitution from Glycine to Arginine. The mutation for G. rugosa and F. kawamurai occurs in exons 1 and 3. The mutations of the third population of P. nigromaculatus, and the mutations of G. rugosa and F. kawamurai occurred in areas that are highly conserved among vertebrates which could result in a dysfunctional tyrosinase gene.^[25]

Evolution

Tyrosinase is a highly conserved protein in animals and apparently arose already in

Lighter skin complexion has been associated with youth and beauty across various Asian cultures. Recent research by cosmetic companies has been focused on the development of novel whitening agents that selectively suppress tyrosinase activity to reduce hyperpigmentation while avoiding cytotoxicity of healthy melanocytes.^[35] Traditional pharmacological agents such as corticosteroids, hydroquinone, and amino numeric chloride lighten skin through the inhibition of melanocyte maturation.^[36] However, these agents are associated with adverse effects. Cosmetic companies have been focused on developing novel whitening agents that selectively suppress the activity of tyrosinase to reduce hyperpigmentation while avoiding melanocyte cytotoxicity as tyrosinase is the rate-limiting step of the melanogenesis pathway.

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 as it is the defensive mechanism of insects. Some insecticides are aimed to inhibit tyrosinase.^[14]

In mussel-glue inspired polymers

Tyrosinase activated