Selenium and hydrogen selenide: essential micronutrient and the fourth gasotransmitter?

Abstract

Selenium (Se) is an essential micronutrient required by organisms of diverse lineage. Dietary Se is converted to hydrogen selenide either enzymatically or by endogenous antioxidant proteins. This convergent biochemical step crucially underlies the subsequent biological activity of Se and argues for inclusion of hydrogen selenide as the fourth endogenous gasotransmitter alongside nitric oxide, carbon monoxide and hydrogen sulfide. Endogenously generated hydrogen selenide is incorporated into numerous 'selenoprotein' oxidoreductase enzymes, essential for maintaining redox-status homeostasis in health and disease. Direct effects of endogenous hydrogen selenide on cellular and molecular targets are currently unknown. Given exogenously, hydrogen selenide acts as a modulator of metabolism via transient inhibition of mitochondrial cytochrome C oxidase. Here we provide an overview of Se biology, its impact on several physiological systems (immune, endocrine, cardiovascular and metabolic) and its utility as a supplement in acute and critical illness states. We further explore the evidence base supporting its role as the fourth gasotransmitter and propose a strategic case towards generation of novel selenomimetic therapeutics.

The Pharmacology and Therapeutic Utility of Sodium Hydroselenide

“…Mindful of the chemical and biological similarities between sulfur and its chalcogen homologue, selenium [ 17 ], we [ 9 ] and others [ 10 ] postulated that its reduced form, hydrogen selenide, could be an additional member of the gasotransmitter class. To explore this hypothesis, we began experimental work using the basic selenide salt, NaHSe.…”

“…Inclusion of any prospective candidate into the gasotransmitter class requires satisfaction of five criteria [ 1 ]. Hydrogen selenide can fulfil the first three criteria, being present as a small molecule of gas [ 17 ], freely permeable to cell membranes [ 23 ], and endogenously generated under regulatory (enzymatic) conditions [ 9 ]. The currently accepted function of hydrogen selenide at physiologically relevant concentrations relates entirely to its incorporation into selenoproteins, and there are no recognized cellular effects that operate via second messengers.…”

“…Their dysfunction and/or dysregulation is implicated in diverse pathologies including diabetes, Alzheimer’s disease, cardiovascular diseases and cancer [ 24 , 25 ]. Incorporation of selenium into selenoproteins requires a uniquely adapted translational machinery that utilizes hydrogen selenide derived either from Se-oxidation products, or enzymatically from selenocysteine [ 9 ].…”

“…Owing to their proximity in the periodic table, sulfur and selenium share several chemical and biological characteristics. We [ 9 ] and others [ 10 ] have postulated that the physiological derivative of selenium, hydrogen selenide (as gaseous H 2 Se and anionic HSe − ), could be an additional member of the gasotransmitter class. Less contentiously, selenium is considered an essential micronutrient [ 11 ] that supports diverse physiological roles, most notably as a structural and functional component of antioxidant ‘selenoproteins’ [ 12 ].…”

A Review of the Potential Health Benefits of Low Alcohol and Alcohol-Free Beer: Effects of Ingredients and Craft Brewing Processes on Potentially Bioactive Metabolites

“…Much of the attention on bioactives contained within the ingredients has focused on the hops (Humulus lupulus); however, a number of grains may also contain compounds which could have potentially beneficial effects on human health including vitamins, minerals and phenolic compounds such as phytoestrogens. One example is that barley grown in some regions is a source of selenium, which is a useful antioxidant in the body and may be more important than was previously thought [12].…”