Selenoproteins and their impact on human health through diverse physiological pathways

Abstract

In the last few decades, the importance of selenium in human health has been the subject of numerous studies. It is believed that the physiological effects of selenium occur mainly through the function of selenoproteins, which incorporate selenium in the form of one or more selenocysteine residues. Recent advances in understanding the complex regulation of selenoprotein synthesis and functional characterization of several members of the selenoprotein family have contributed to an improved comprehension of the role(s) of selenium in human health and the great diversity of physiological pathways influenced by this trace element.

FIGURE 1

Schematic showing cis- and trans-acting elements required for selenocysteine incorporation into selenoproteins

FIGURE 2. Biochemical and physiological roles of selenoproteins

Major known activities and roles for the 25 selenoproteins identified in humans are indicated. Many proteins likely have multiple other functions not indicated here. Involvement in oxidoreduction reactions is a unifying feature of this protein family; however, there is great diversity in tissue distribution and physiological pathways where these reactions occur. The biochemical activities and/or physiological roles of more than half these proteins remain unknown. CNS, central nervous system.

FIGURE 3. Selenoprotein P knockout mouse phenotypes

Interactions between genotype and environmental factors are evident in Sepp1 knockout mice, whose severe phenotype can be ameliorated by nutritional supplementation with a high selenium diet.