Seleninic Acid Research Articles

Structure analysis and molecular model of the selenoenzyme glutathione peroxidase at 2.8 Å resolution

The three-dimensional structure of bovine erythrocyte glutathione peroxidase, a tetrameric enzyme containing 4 gram atoms of selenium per mole ( M r = 84,000), has been determined at 2.8 Å resolution using the multiple isomorphous replacement method. By correlation calculations in Patterson space the tetramers were shown to exhibit molecular [222] symmetry, proving the monomers to be identical or at least very similar. The monomer consists of a single polypeptide chain of 178 amino acid residues. Its shape is nearly spherical with a radius of r ≈ 19 A ̊ . A tentative sequence corresponding to a partially refined model ( R = 0.38) is given. Each subunit is built up from a central core of two parallel and two anti-parallel strands of pleated sheet surrounded by four α-helices. One of the helices runs antiparallel to the neighbouring β-strands giving rise to a βαβ substructure, an architecture that has been found in several other proteins e.g. flavodoxin, thioredoxin, rhodanese and dehydrogenases. A comparison of the glutathione peroxidase subunit structure with thioredoxin-S 2 revealed large regions of structural resemblance. The central four-stranded β structure together with two parallel α-helices resembles nearly 80% of the thioredoxin fold. The active sites of glutathione peroxidase are located in flat depressions on the molecular surface. Probably each active centre is built up by segments from two subunits. The catalytically active selenocysteines were found at the N-terminal ends of long α-helices and are surrounded by an accumulation of aromatic side-chains. A difference Fourier map between oxidized and substrate-reduced glutathione peroxidase as well as heavy-atom binding led to the conclusion that the two-electron redox-cycle involves a reversible transition of the active-site selenium from a selenenic acid (RSeOH) to a seleninic acid (RSeOOH).

Donor substrate specificity and thiol reduction of glutathione disulfide peroxidase.

By isolation of a mixed disulfide product of glutathione and cysteine, glutathione peroxidase was shown to be highly specific for only one donor substrate. Using the coupled assay of NADPH and yeast glutatione reductase, which is highly specific for flutathione disulfide, it was shown that the apparent inhibition of glutathione peroxidase by mercaptoethanol can be described kinetically and that it is competitive with glutathione. Also, when limiting amounts of hydroperoxide were present in the reaction mixture with mercaptoethanol or cysteine, the total amount of glutathione disulfide produced decreased as compared with that in a reaction mixture without mercaptoethanol or cysteine. This finding is consistent with enzymatic formation of mixed disulfides. Data presented suggest that the selenium in glutathione peroxidase was oxidized to a seleninic acid in the absence of glutathione. These results can be explained by a mechanism for glutathione peroxidase wherein the selenium atom is the only atom in the enzyme that undergoes oxidation reduction.

Oxidation of Amines with Benzeneseleninyl Chloride

Abstract Seleninic acid derivatives of the type (1) and ( )2o (2) have been shown to undergo nucleophilic attack on Se by enolate anions1,2 and phenols.2 In the case of enolate anions, the resulting α-keto selenoxide readily eliminates PhSeOH, to effect a net oxidation by introducing a double bond α to the carbonyl.3 It has been demonstrated that 2 reacts readily with certain primary amines, presumably through a similar pathway (i.e. elimination of PhSeOH from an intermediate seleninamide (3))4. This paper describes the analogous reaction of 1 with amines (Scheme I).

Biological potency of organic selenium compounds: VI. Aliphatic seleninic acids and carboxyseleninic acids

Straight-chain aliphatic seleninic acids, CH 3-(CH 2) n -SeOOH, with chain lengths from C 4 to C 17, a few dibasic acids of moderate chain length having seleninic acid groups on both ends of the molecule, HOOSe-(CH 2) n -SeOOH, and a series of carboxyseleninic acids, HOOC-R-SeOOH, comprising chain lengths from C 3 to C 13 and several branched chains with 5 to 7 carbon atoms were tested for potency in the prevention of dietary liver necrosis in the rat. Alkylseleninic acids showed uniformly low activities, ranging from 18% to 56% of that of selenite selenium which served as a standard. There were no discernible trends or regularities with increasing chain lengths, in contrast to other series of alkylselenium compounds. It is therefore unlikely that alkylseleninic acids are normal oxidation products of dialkyl mono- or diselenides in the organism. Compounds with seleninic acid groups at both ends of the chain were practically inactive. Carboxyseleninic acids carrying a carboxyl group distal to the seleninic acid group, on the other hand, were highly effective. A maximum of potency occurred at chain lengths C 3 and C 4, followed by a sharp decline between C 4 and C 6. A second maximum of activity occurred at C 6. There was no alternating effect. This structure/activity pattern is analogous to that of the diselenodicarboxylic acids. However, the lower carboxyseleninic acids were, per atom of selenium, twice as active as the corresponding diseleno-dicarboxylic acids, of which the higher members were less potent. It is inferred that carboxyseleninic acids may be metabolically related to diseleno-dicarboxylic acids and that C 3 and C 4 carboxyseleninic acids may play a physiological role.

Selenium dioxide oxidations of olefins. Trapping of the allylic seleninic acid intermediate as a seleninolactone

Selenium dioxide oxidations of olefins. Trapping of the allylic seleninic acid intermediate as a seleninolactone

A study of some benzeneseleninic acids; kinetics of reduction by iodide ion

The kinetics of the redox reaction of some para- and meta-substituted benzeneseleninic acids with iodide ion in acidic aqueous ethanol are reported. The acids are reduced to diaryl diselenides with the uptake of 3 equiv. of iodide ion. The reduction is of the first order in seleninic acid, iodide, and hydrogen ion. The rate constants at 25 ± 0·1°C for the H, p-Cl, p-Br, p-NO2, p-Me, m-Cl, m-Br, and m-NO2 derivatives are also reported.