Bioactivation of chemopreventive selenocysteine Se-conjugates and related amino acids by amino acid oxidases novel route of metabolism of selenoamino acids

Several selenocysteine Se-conjugates have been shown to possess potent chemopreventive activity in animal models for chemical carcinogenesis. As a mechanism of action, β-elimination reactions to form chemopreventive selenols, ammonia, and pyruvate has been proposed. The enzymes involved in these β-elimination reactions, however, have been partially elucidated. Next to cysteine conjugate β-lyases, as yet unidentified non-pyridoxal-5′-phosphate-dependent enzymes also appear to be involved in cytosolic β-elimination reactions. In the present study, it was investigated whether amino acid oxidases contribute to the bioactivation of selenocysteine Se-conjugates. Using purified L-amino acid oxidase from Crotalus adamanteus as a model enzyme, significant β-elimination activities were indeed observed upon incubation with Se-methylselenocysteine (