Tyrosinases

L-tyrosine phenol + pyruvic acid + NH P-tyrosinase Erwinia herbicola ... 

Genetic disruption of dopamine synthesis in mice lacking TH shows that dopamine is not essential for development. However, dopamine deficient mice do not survive long after weaning unless treated with l-DOPA. These mice display severe aphagia and adipsia and loss of motor function. While these mice have a major reduction in dopamine levels some residual dopamine can be detected that is generated through the action of tyrosinases. 

The early works by Muzzarelh et al. [179] showed that tyrosinase converts a wide range of phenohc substrates into electrophihc o-quinones [180]. Tyrosinase was used to convert phenols into reactive o-quinones which then underwent chemical reactions leading to grafting onto chitosan. A review article showed that in general the tyrosinase-catalyzed chitosan modifications resulted in dramatic changes in functional properties [181]. 

An interesting combination of enzymatic with non-enzymatic transformation in a one-pot three-step multiple sequence was reported by Waldmann and coworkers [82]. Phenols 125 in the presence of oxygen and enzyme tyrosinase are hydroxylated to catechols 126 which are then oxidized in situ to ortho quinones 127. These intermediates subsequently undergo a Diels-Alder reaction with inverse electron demand by reaction with different dienophiles (Table 4.19) to give endo bicyclic 1,2-diketones 128 and 129 in good yields. 

Table 4.19 Multiple hydroxylation-oxidation Diels-Alder reactions initiated by tyrosinase...

Among these factors, sun exposure remains the most important, although all of them significantly increase the activity of tyrosinase in producing melanin. 

Azelaic acid is a non-phenolic derivative (1,7-hep tanedicarboxylic acid) used at concentration of 10-20% twice a day to treat melasma with minimal side effects (allergic reactions). It acts to disturb the tyrosinase synthesis and can be used as a bleaching agent in patients sensitive to hydroquinone. Better results are obtained if a glycolic acid cream is applied sequentially to azelaic acid treatment. 

Kojic acid is a fungal metabolite (5-hydroxy-4 pyran 4-1-2 methyl) known to inhibit tyrosinase and used to treat melasma at concentration of 2-4% twice a day. The stability is one of its advantages if compared with hydroquinone. Unfortunately, it is considered to have a high sensitizing potential. 

Azelaic acid is a naturally occurring dicarboxyl-ic acid (1,7-heptanedicarboxylic acid) that has demonstrated beneficial therapeutic effects in the treatment of acne and several disorders of hyperpigmentation [48]. There are minimal effects on normally pigmented human skin, freckles, senile lentigines, and nevi. The cytotoxic and antiproliferative effects of azelaic acid may be mediated via inhibition of mitochondrial ox-idoreductase activity and DNA synthesis. Disturbance of tyrosinase synthesis by azelaic acid may also influence its therapeutic effects. Azelaic acid can be used as a hypopigmenting agent in patients sensitive to hydroquinone. 

Kojic acid (5-hydroxy-4 pyran 4-1-2 methyl) is a fungal derivative which inactivates tyrosinase via chelation of copper. Concentrations range from 2 to 4%. It can be used for monotherapy or in combination with retinoids or other cosme-ceutical products such as glycolic acid. Compared with hydroquinone, these kojic acid formulations usually show less efficacy. However, they may be effective in patients who do not... 

The oxidation of phenol in alcoholic media by a morpholine complex of Cu(II) (as a model for tyrosinase) to give 4,5-dimorpholino-orr/jo-benzoquinone in 64 %... 

Gandia-Herrero, R, Escribano, J., and Garci a-Carmona, R, Betaxanthins as substrates for tyrosinase an approach to the role of tyrosinase in the biosynthetic pathway of betalains. Plant Physiol, 138, 421, 2005. 

Steiner, U., Schhemann, W., and Strack, D., Assay for tyrosine hydroxylation activity of tyrosinase from betalain-forming plants and cell cultures, Anal. Biochem., 238, 72, 1996. 

Melanin biosynthesis in animals is a complex process starting with the L-tyrosine amino acid. In the first step, L-tyrosine is converted first into DOPA and then into dopaquinone, a process catalyzed by tyrosinase. In the biosynthesis of eumelanins, dopaquinone undergoes a cyclization to form dopachrome and subsequently a tau-tomerization into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). DHICA is further oxidized to indole-5,6-quinone2-carboxylic acid, the precnrsor of DHICA eumelanins. Tyrosinase-related proteins TRP-2 and TRP-1, respectively, are responsible for the last two steps, and they are under the control of the tyrosinase promoter. 

Murisier, F. and Beerman, F., Genetic of pigment cells lessons from the tyrosinase gene family, Histol. HistopathoL, 21, 567, 2006. 

Gandia-Herrero, P., Escribano, J., and Garcla-Carmona, P., Characterization of the activity of tyrosinase on betaxanthins derived from (iJ)-amino acids, J. Agric. Food Chem., 53, 9207, 2005. 

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