Differences in subcellular distribution of catechol-O-methyltransferase and tyrosinase in malignant melanoma

The activities of catechol-O-methyltransferase (COMT) and tyrosinase were measured in subcellular fractions obtained from transplantable melanotic and amelanotic hamster melanoma. The results showed that there was a substantial difference between the localization of these enzymes. Whereas tyrosinase was localized mainly in the large granule fraction, the highest COMT activity was found to be in fractions abundant in microsomal structures. As expected, subcellular fractions obtained from amelanotic melanoma contained low or undetectable tyrosinase activity. On the other hand, the same fractions exhibited higher COMT activity than those from the pigmented tumor. Relatively low specific activity of COMT in fractions containing coated vesicles does not support the idea that this enzyme could be responsible for the inhibition of melanin polymerization in these structures. Because melanogenic intermediates, such as 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid, are compartmentalized within membraneous structures, the preferential localization of COMT in cytosol and cytosolic membrane network might be advantageous for a detoxification role in (melanotic) melanocytes that produce dihydroxyindoles.