A revised concept of mammalian melanogenesis: the possible synergistic functions of aerobic dopa oxidase and peroxidase. A review.

The enzymatic oxidation of tyrosine to melanin in mammalian cells is widely believed to be mediated solely by an aerobic, copper-dependent enzyme called tyrosinase (1). This enzyme is considered to be analogous to the tyrosinase of plants and insects, which has been shown to mediate the first two steps of the tyrosine to melanin sequence (2-4): hydroxylation of tyrosine to dopa and oxidation of dopa to dopa quinone. This hypothesis superseded that of Bloch (5) which held that the key enzyme in melanogenesis was a specific dopa oxidase which was incapable of oxidizing tyrosine. Bloch's hypothesis prevailed until several decades ago when Lerner et al. (6) published their initial studies, which used manometric data obtained from crude extracts of mouse melanoma to provide evidence for the existence of a mammalian tyrosinase. These authors expressed the opinion that failure of Hogeboom and Adams (7) and Greenstein and Algire (8) to demonstrate activity toward tyrosine in their "dopa oxidase" melanoma fractions was because of their unawareness of the role of dopa as a required cofactor. Other authors (9, 10), using similar methods, reported results corresponding to those of Lerner et al. (6). More recent studies with incompletely purified enzyme preparations from mammalian melanomas supporting the "tyrosinase" hypothesis include those of Pomerantz (11-13) and Miyazaki and Seiji (14). Burnett (15) has described a highly purified "tyrosinase" preparation from mouse melanoma, but omitted data pertaining to the ability of this preparation to utilize tyrosine. Fitzpatrick et al. described the histochemical demonstration of "tyrosinase" in normal and neoplastic melanocytes using unlabeled (16) and labeled (17) substrates. Both studies involved prolonged incubation of tissue in tyrosine without