Phaeomelanin biosynthesis

The involvement of cysteine in the biosynthesis of phaeomelanins and trichochromes, natural pigments in mammals, has prompted work on the reaction of cysteine with a variety of reagents to produce the 1,4-benzo-thiazine ring system. 

The intramolecular cyclodehydration of orf/zo-quinones with a (2-aminoethyDthioether substituent at position 3 leads to benzothiazine derivatives (equation (19)) and is an important feature of the biosynthesis of phaeomelanin pigments from 5-cysteinyldopa 137 (Scheme 35). The chemistry of the cyclisation of the quinone 138 and related model compounds has been reviewed (92MI1,01JPPB123,06MI282). For further examples see Section 3.1.4.2. 

At present, little is known about the biologic conditions which determine the ratio of formation of phaeomelanins and tricho-chromes in different mammalian species. But it is noteworthy that, while in model experiments the cysteinyldopas are smootly converted into phaeomelanin-like pigments by the action of tyrosinase in the presence of dopa as co-factor, attempts to convert them into tri-chochromes under similar conditions have been so far unsuccessful. Thus, it seems that the later stages in the biosynthesis of tricho-chromes require certain specific biochemical conditions which, however, remain elusive. 

All this biochemical information points to a general role of the glutathione system in the metabolic activity of both eumelanic and phaeomelanic melanocytes. Hov/ever, whether glutathione is also specifically involved in the biosynthesis of the cysteinyldopas required for phaeomelanin formation remains to be determined, and the answer obtained will unquestionably contribute to our understanding of the synthetizing activity of mammalian melanocytes. 

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