Isolation, characterization and thiol exchange reaction of penicillamine selenotrisulfides

doi:10.1016/0006-291X(86)90960-5

Biochemical and Biophysical Research Communications

Volume 135, Issue 1, 26 February 1986, Pages 183-188

https://doi.org/10.1016/0006-291X(86)90960-5 Get rights and content

Abstract

Penicillamine selenotrisulfides formed by the reaction of selenite with D-, L-, and DL-penicillamines in the aqueous solution have been isolated and submitted to the spectroscopic and chromatographic analyses. FAB-MS spectra indicated the molecular ion peak (M+1)⁺ at $m z$ 377, which confirmed the molecular formula(C₁₀H₂₀N₂O₄S₂Se) for all these selenotrisulfides. The [⁷⁷Se]NMR and HPLC results showed that symmetric selenotrisulfides (DD and LL) were formed from D- and L-penicillamines, respectively, while asymmetric selenotrisulfide (DL) in addition to symmetric ones was formed from DL-penicillamine. The occurrence of thiol exchange reaction of selenotrisulfides was verified.

References (5)

H.E. Ganther
Biochem
(1971)
E.P. Painter
Chem. Rev
(1941)

There are more references available in the full text version of this article.

Cited by (22)

High affinity selenium uptake in a keratinocyte model
2008, FEBS Letters
The distribution of selenium in mammals has been recently shown to be mediated primarily by selenoprotein P. Even in the absence of selenoprotein P, selenium is distributed from the liver into all organs and tissues when supplemented in the diet. The form of selenium that is actively taken up by mammalian cells at trace concentrations has yet to be determined. We used a human keratinocyte model to determine whether reduction of the oxyanion selenite $({SeO}_{3}^{2 -})$ to the more reduced form of selenide (HSe⁻) would affect uptake. Indeed a reduced form of selenium, presumably selenide, was actively transported into keratinocytes and displayed saturation kinetics with an apparent K_m of 279 nM. ATPase inhibitors blocked the uptake of selenide, as did the competing anions molybdate and chromate, but not sulfate. These results suggest that the small molecule form of selenium that is distributed in tissues is hydrogen selenide, despite its sensitivity to oxygen and reactivity to thiols.
Selenium binding to human hemoglobin via selenotrisulfide
2005, Biochimica et Biophysica Acta - General Subjects
Selenotrisulfide (e.g., glutathione selenotrisulfide (GSSeSG)) is an important intermediate in the metabolism of selenite. However, its reactivity with biological substances such as peptides and proteins in the subsequent metabolism is still far from clearly understood, because of its chemical instability under physiological conditions. Penicillamine (Pen) is capable of generating a chemically stable and isolatable selenotrisulfide, PenSSeSPen. To explore the metabolic fate of selenite in red blood cells (RBC), we investigated the reaction of selenotrisulfide with human hemoglobin (Hb) using PenSSeSPen as a model. PenSSeSPen rapidly reacted with Hb under physiological conditions. From the analysis of selenium binding using the Langmuir type binding equation, the apparent binding number of selenium per Hb tetramer almost corresponded to the number of reactive thiol groups of Hb. The thiol group blockade of Hb by iodoacetamide treatment completely inhibited the reaction of PenSSeSPen with Hb. In addition, MALDI-TOF mass spectrometric analysis of the selenium-bound Hb revealed that PenSSe moiety binds to the β subunits of Hb. Overall, the reaction of PenSSeSPen with Hb appears to involve the thiol exchange between Pen and the cysteine residues on the β subunit of Hb.
Selenium-77 nuclear magnetic resonance spectroscopy
1995, Progress in Nuclear Magnetic Resonance Spectroscopy
Inhibition of rat brain prostaglandin D synthase by inorganic selenocompounds
1991, Archives of Biochemistry and Biophysics
Various inorganic selenocompounds dose-dependently inhibited the rat brain prostaglandin (PG) D synthase, both in the purified enzyme preparation and in the crude brain supernatant. All of the quadrivalent selenium compounds tested had a very limited range of IC₅₀ values in the purified enzyme (11–12 μm) and in the brain supernatant (9–15 μm). A divalent selenium compound was also inhibitory, but a hexavalent selenium compound was ineffective. In contrast, organic selenocompounds such as selenomethionine and selenourea had no effect on the PGD synthase activity. Furthermore, sodium sulfate and sodium sulfite up to 10 mm did not inhibit the activity. The inhibition by selenium required the preincubation of the metal with sulfhydryl compounds such as dithiothreitol (DTT), indicating that the formation of selenotrisulfide or some other adduct(s) is essential for the inhibition. Furthermore, the inhibition was reversed by an excess amount of dithiothreitol, suggesting that the selenotrisulfide derivative of DTT binds to the SH group of the PGD synthase. The kinetic analysis revealed the inhibition by selenite to be noncompetitive with a K_i value of 10.1 μm. On the other hand, glutathione-dependent PGD synthase from rat spleen was much less inhibited, and PGF synthase and PGD₂ 11-ketoreductase activities were not inhibited by the selenium compound.
Separation and detection of Bis(Alkylthio)selenides of penicillamine and glutathione by liquid chromatography with electrochemical detection
1989, Journal of Chromatography A
Sensitive and selective methodology is described for the simultaneous determination of thiols, disulfides and bis(alkylthio)selenides in mixtures formed by reaction of selenious acid with thiols. The methods are based on separation of the various compounds by reversed-phase ion pairing chromatography followed by detection with an electrochemical detector equipped with dual mercury/gold amalgam electrodes in series in the eluent stream. Thiols are detected directly at the downstream electrode. Bis(alkylthio)selenides and disulfides are detected indirectly by first reducing them at the upstream electrode followed by detection of the reduction products at the downstream electrode. Bis(alkylthio)selenides are reduced at less negative potentials than disulfides, making it possible to selectively detect them in mixtures with disulfides. Detector response to bis(penicillamine)selenides is linear from 1.1 · 10^-7 M up to at least 1.2 · 10^-4 ^M; the detection limit is estimated to be < 2 pmol bis(penicillamine)selenide.
Thiol exchange reactions involving selenotrisulfides
1988, Biochemical and Biophysical Research Communications
The occurrence of in vitro thiol exchange reactions involving selenotrisulfides has been documented by HPLC analyses of reaction solutions. Asymmetric selenotrisulfide(RSSeSR') (R,R' = penicillamine, cysteine, glutathione) was formed by the reactions between (i) a mixture of thiols and selenite, (ii) thiol(R'SH) and symmetric selenotrisulfide(RSSeSR), and (iii) symmetric selenotrisulfides(RSSeSR and R'SSeSR'). Further reaction of an asymmetric selenotrisulfide with thiol(R'SH) produced another symmetric selenotrisulfide(R'SSeSR'). These thiol exchange reactions may offer significant information to elucidate intake and metabolism of selenium in vivo.

View all citing articles on Scopus

View full text

Isolation, characterization and thiol exchange reaction of penicillamine selenotrisulfides

Abstract

Biochem

Chem. Rev