Chapter 40 - Soft electrophile inhibition of selenoenzymes in disease pathologies

Abstract

Electrophiles are abundant in diets and environmental exposures, but their effects on selenium (Se) metabolism have only begun to be studied. Selenium-dependent enzymes depend on the functions of selenocysteine (Sec) to perform their biochemical roles. As the most potent intracellular nucleophile, Sec is subject to binding by mercury and other electron-poor soft neurotoxic electrophiles. Humans possess 25 selenoprotein genes, approximately half of which are engaged in preventing, controlling, or reversing oxidative damage. While selenoproteins are expressed in tissue-dependent distributions and levels in all cells of all vertebrates, they are particularly important in brain development, health, and functions. Additional study is required to examine possibilities of inherited, acquired, or degenerative disorders of Se homeostasis that may influence neurological and cardiovascular vulnerability to soft electrophile exposures. Since selenoenzymes are molecular “targets” of soft electrophiles, concomitant evaluation of aggregate exposures to these toxicants must be assessed in relation to dietary Se intakes.