Dihydroxyindole blocking factor

According to Pawelek et al. 200), the biosynthesis of melanin in Cloudman melanoma cells is a complex process and is regulated by three factors (a) a dopamine conversion factor which converts dopamine to 5,6-dihydroxyindole (13), (b) a 5,6-dihydroxyindole conversion factor which catalyzes the conversion of 5,6-dihydroxyindole to melanin and is active when cells are exposed to melanotropin (MSH), and (c) a 5,6-dihydroxyindole blocking factor which restricts melanogenesis at the 5,6-dihydroxyindole stage. They have also shown that at least three steps in the Raper-Mason scheme of melanin formation from tyrosine are catalysed by tyrosinase (Fig. 6). 

For many years the biosynthesis of melanin was thought to result from the spontaneous oxidation and polymerization of dopachrome produced by the tyrosinase-catalyzed hydroxylation of tyrosine to dopa and subsequent oxidation (5 ). In addition to tyrosinase, however, several enzymatic factors have been recently identified in mammalian tissues that appear to regulate melanogenesis at intermediate steps distal to those involving tyrosine and dopa. The factors include dopachrome conversion factor, dihydroxyindole blocking factor, dihydroxyindole conversion factor and dopachrome oxidoreductase (54-59). 

Dihydroxyindole blocking factor blocks the indolization of quinone imine derivatives. Dihydroxyindole conversion factor catalyzes the dehydrogenation of 5,6-dihydroxyindole to indole-5,6-qui-none. Dopachrome oxidoreductase converts dopachrome to 5,6-dihydroxyindole and also may block 5,6-dihydroxyindole oxidation and subsequent melanogenic reactions. Relatively little information is available about the physical, chemical and kinetic properties of these proteinaceous factors in mammals. Controversy about melanin-related regulatory factors has focused on whether activity is due to unique individual proteins or is only an expression of activities of a multicatalytic enzyme (61.62). For example, dihydroxyindole conversion activity in mice melanoma is apparently due to tyrosinase, not a unique factor (56). 

---