Selenium-containing enzymes in mammals: Chemical perspectives

Abstract

The chemical and biochemical route to the synthesis of the 21st amino acid in living systems, selenocysteine, is described. The incorporation of this rare amino acid residue into proteins is described with emphasis on the role of monoselenophosphate as selenium source. The role of selenocysteine moiety in natural mammalian enzymes such as glutathione peroxidase (GPx), iodothyronine deiodinase (ID) and thioredoxin reductase (TrxR) is highlighted and the effect of other amino acid residues located in close proximity to selenocysteine is described. It is evident from various studies that two amino acid residues, tryptophan and glutamine, appear in identical positions in all known members of the GPx family. According to the three-dimensional structure established for bovine GPx, these residues could constitute a catalytic triad in which the selenol group of the selenocysteine is both stabilized and activated by hydrogen bonding with the imino group of the tryptophan (Trp) residue and with the amido group of the glutamine (Gln) residue. The ID enzymes, on the other hand, do not possess any Trp or Gln residues in close proximity to selenium, but contain several histidine residues, which may play important roles in the catalysis. The TrxR enzymes also possess some basic histidines, but the most important amino acid residues are the cysteines which constitute the internal cofactor systems along with the catalytically active selenocysteine. The catalytic activity and substrate specificity of all three selenoenzymes are described. The reactivity of selenocysteine residues in selenoenzymes towards metal-based drugs such as goldthioglucose is also described.

Crystal Structures of a Poplar Thioredoxin Peroxidase that Exhibits the Structure of Glutathione Peroxidases: Insights into Redox-driven Conformational Changes

“…In mammals, GPXs that form a group of enzymes with an important role in protecting cells against ROS, using GSH as the reducing substrate, have been studied extensively. 6 In plants, different isoforms of GPX are found to be expressed in various subcellular compartments. Recently, one of these GPXs was proposed to play a role in signal transduction during stress conditions.…”

Evaluation of Biofield Energy Treatment on Physical and Thermal Characteristics of Selenium Powder

“…In XRD pattern of control sample, peaks were observed at 2θ equal to 23 [18]. In addition, the intense peaks in control and treated sample suggested the crystalline nature of selenium powder.…”

“…It is reported that selenium reacts with various enzymes due to its redox nature i.e. it can oxidise as well as reduce the enzymes [23]. Further, in biological activities, the interatomic interaction of selenium plays a major role.…”

Water-dependent synthesis of biologically active diaryl diselenides

“…Glutathione peroxidase (GPx) is a selenoenzyme that, based on the presence of catalytically active aminoacid selenocysteine (Sec, U), eliminates reactive oxygen and nitrogen species enabling to maintain the redox homeostasis inside the cell. 25,26 It is assumed that the most-studied GPx mimic ebselen (Nphenylbenzisoselenazo-3(2H)-one, 1), through the reaction with thiols, can be transformed to the corresponding diaryl diselenide with amido function 2 and in this form act as a bio-active intermediate that eliminates peroxides. [27][28][29] It has been proven that Se-N bond is not necessary to observe an enhanced GPx-like activity.…”