Half-lives of tyrosinase isozymes from Harding-Passey mouse melanoma

The half-lives of tyrosinase isozymes, a key enzyme in melanogenesis, have been determined using two different approaches: (a) cycloheximide treatment of mice bearing growing tumors and measurement of the residual enzymatic activity. This approach detected two soluble forms of cytosolic tyrosinase with half-lives of 1/2 and 8 h, respectively. The melanosomal isozyme showed a t1/2 of 3 1/2 h. (b) Metabolic labelling of tyrosinase with [35S]Met and immunoprecipitation analysis using a monoclonal antityrosinase. This method gave values slightly longer, 5 h and 9 1/2 h for the melanosomal and cytosolic tyrosinase, respectively. The origin of soluble tyrosinase and its utility to employ that enzymatic activity in melanoma chemotherapy using catechols as tyrosinase-dependent precursors of cytotoxic quinones is discussed.