1242 Suicide substrate properties of rhododendrol are responsible for tyrosinase inactivation and melanocyte death

Tyrosinase catalyzes the initial, rate-limiting step of melanin synthesis; oxidative conversion L-tyrosine to L-dopa followed by L-dopaquinone means oxygen molecule. possesses bicopper active center capable utilizing molecular oxygen. Metabolic rhododendrol (RD) tyrosinase causes leukoderma in a certain population consumers. Along with cytotoxic RD metabolites, reactive species (ROS) produced during metabolism appears cause melanocyte death. However, actual source for ROS is still elusive. Some phenolic compounds are known act as suicide substrates tyrosinase, and, catalytic reaction, one two copper ions along hydrogen peroxide released from tyrosinase. We hypothesized that might be potent substrate and ion responsible Incubation human melanocytes showed decrease activity. Among three strains melanocytes, strain highest activity was most susceptible RD-induced cell Inhibitors apoptosis or ferroptosis did not significantly alleviate Both inhibitor phenylthiourea (PTU) chelator D-penicillamine (DPA) alleviated PTU irreversibly inhibited whereas DPA had no effects on enzymatic The protective effect due its ability chelate rather than direct inhibition result release production peroxides, which collectively damages melanocyte. These observations suggest chelation may become general prevention chemical caused aberrant