Substrate Limiting Melanogenic Inhibitor in Malignant Melanomas

Abstract

THE presence of a heat stable, tyrosinase-inhibiting factor in various malignant melanomas has recently been reported^1–4. The reported inhibitor (s) has been partially purified and its mode of action has been determined to be competitive. Although it was not determined whether competition was with enzyme or substrate, the presence of a tyrosine residue within this factor seemed to suggest competition with substrate. We report here the presence of a separate, heat labile inhibitory substance within malignant melanoma tissue which is competitive with tyrosinase, that is, it competes with tyrosinase for the substrates tyrosine and 3,4 dihydroxyphenylalanirie (dopa). The independence of this inhibitory activity from either added pyridoxal phosphate or α-methyldopa, from ATP, and furthermore, its absence in normal hamster liver⁵, provides evidence that it is not due to either tyrosine or dopa decarboxylase or transaminase, or in vitro protein synthesis.