TYROSINASE AND γ‐GLUTAMYL TRANSPEPTIDASE IN 5‐S‐CYSTEINYLDOPA GENESIS WITHIN MELANOTIC AND AMELANOTIC MELANOMAS

Publisher Website
Google Scholar
Abstract
The roles of tyrosinase and γ‐glutamyl transpeptidase (γ‐GTP) in 5‐S‐cysteinyldopa (5‐S‐CD) genesis in melanotic and amelanotic melanoma cells has been investigated in vitro and in vivo. Complete inhibition of tyrosinase by 10–3 M diethyl dithiocarbamate has been found to partially inhibit dopa‐cysteine dependent 5‐S‐CD genesis by cultured melanoma cells. On the other hand iodoacetamide, an inhibitor of γ‐GTP, has been found to completely inhibit dopa‐glutathione dependent 5‐S‐CD genesis by these cells. Melanotic melanoma has been found to be rich in tyrosinase and γ‐GTP activity. In contrast, the amelanotic melanoma studied here was found to lack tyrosinase activity and to have very little γ‐GTP activity. The sub‐cellular distribution of these enzymes in melanotic melanoma cells has revealed that while the melanosome‐rich fraction is high in tyrosinase activity, it contains no substantial γ‐GTP activity. These findings indicate that 5‐S‐CD can form non‐enzymically in vitro from dopa and cysteine. Further, it also provides evidence that γ‐GTP is the enzyme that converts glutathione‐dopa to 5‐S‐CD within melanoma cells.