19] Enzymatic pathways of β elimination of chemopreventive selenocysteine Se conjugates

Abstract

Publisher Summary Three naturally occurring selenocysteine Se conjugates (SeCys conjugates), Se-methyl-DL-selenocysteine, Se-(n-propyl)-DL - selenocysteine, and Se-allyl-DLselenocysteine, are relatively potent chemopreventive agents in methylnitrosourea and dimethylbenz[a]anthracene rat mammary tumor models. Enzymes involved in the formation of pharmacologically active selenium metabolites from SeCys conjugates and the assays to measure their respective enzyme activities are described in this chapter. The chapter describes experimental procedures used to investigate the β elimination of SeCys conjugates by cysteine conjugate β-lyases. The chapter also demonstrates that SeCys conjugates are metabolized by at least three different enzyme systems—namely, cysteine conjugate β-lyase/GTK, L-AAO, and FMO. Four biologically active products can be formed from SeCys conjugates by these enzymes: selenols, selenenic acids, selenoxides, and hydrogen peroxide. Theoretically, seleninic acids, of which methylseleninic acid displays chemopreventive activity, can also be formed via oxidation of selenenic acids by hydrogen peroxide.