Selenotrisulfides.  Formation by the reaction of thiols with selenious acid

Ganther, Howard E.

doi:10.1021/bi00848a029

Cited by 348 publications

(172 citation statements)

References 16 publications

(10 reference statements)

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“…As a result of his initial work, this reaction later became known as the Painter reaction. Ganther (2), using reduced glutathione as the thiol, successfully isolated selenodiglutathione (GSSeSG), which was formed on reacting glutathione with selenite in a molar ratio of 4:1 under acidic conditions, thus corroborating the results of Painter. The first detailed reaction mechanism for the Painter reaction was proposed by Kice et al (3), who used a butanethiol derivative as a model compound.…”

supporting

confidence: 64%

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Synthesis and characterization of selenotrisulfide-derivatives of lipoic acid and lipoamide

Self

Tsai

Stadtman

2000

Proc. Natl. Acad. Sci. U.S.A.

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Thiol-containing compounds, such as glutathione and cysteine, react with selenite under specific conditions to form selenotrisulfides. Previous studies have focused on isolation and characterization of intermolecular selenotrisulfides. This study describes the preparation and characterization of intramolecular selenotrisulfide derivatives of lipoic acid and lipoamide. These derivatives, after separation from other reaction products by reverse-phase HPLC, exhibit an absorbance maximum at 288 nm with an extinction coefficient of 1,500 M ؊1 ⅐cm ؊1 . The selenotrisulfide derivative of lipoic acid was significantly stable at or below pH 8.0 in contrast to several other previously studied selenotrisulfides. Mass spectral analysis of the lipoic acid and lipoamide derivatives confirmed both the expected molecular weights and also the presence of a single atom of selenium as revealed by its isotopic distribution. The selenotrisulfide derivative of lipoic acid was found to serve as an effective substrate for recombinant human thioredoxin reductase as well as native rat thioredoxin reductase in the presence of NADPH. Likewise, the lipoamide derivative was efficiently reduced by NADHdependent bovine lipoamide dehydrogenase. The significant in vitro stability of these intramolecular selenotrisulfide derivatives of lipoic acid can serve as an important asset in the study of such selenium adducts as model selenium donor compounds for selenophosphate biosynthesis and as rate enhancement effectors in various redox reactions.

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supporting

confidence: 64%

“…Previously isolated selenotrisulfides, such as GSSeSG, are relatively unstable at physiological (neutral) pH (2,3). The stability of LASe, 0.27 mM, in aqueous buffers of varying pH value during 15 min at 25°C is shown in Fig.…”

Section: Stability Of Lase At Varying Ph Valuesmentioning

confidence: 98%

Synthesis and characterization of selenotrisulfide-derivatives of lipoic acid and lipoamide

Self

Tsai

Stadtman

2000

Proc. Natl. Acad. Sci. U.S.A.

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“…It was previously been argued that the toxicity of organic selenium compounds may occur via oxidation of organic selenium to inorganic selenite. If selenite is generated in vivo, it would be expected to cause oxidation of glutathione and other thiol compounds, resulting in toxicity (Tsen & Tappel 1958;Ganther 1968Ganther & 1971Frost 1972). However, the results of total non-protein thiol groups obtained in the present study indicate that if selenite is being formed from the metabolism of (PhSe) 2 , it does not interact with reduced glutathione.…”

Section: Discussionmentioning

confidence: 52%

“…The aim of this study was to investigate the effect of exposure to (PhSe) 2 and Na 2 SeO 3 , two selenium compounds that oxidize sulfhydryl groups (Tsen & Tapel 1958;Ganther 1968Ganther & 1971Barbosa et al 1998;Maciel et al 2000), into cerebral and hepatic (enzyme) ALA-D and whether simultaneous administration of ascorbic acid, a classical antioxidant, could protect ALA-D inhibition and other toxic signs caused by selenium. The effect of these compounds on selenium distribution, on total non-protein-thiol, ascorbic acid content and haemoglobin was also examined.…”

mentioning

confidence: 99%

Diphenyl Diselenide and Ascorbic Acid Changes Deposition of Selenium and Ascorbic Acid in Liver and Brain of Mice

Jacques-Silva

Nogueira

Broch

et al. 2001

Pharmacology & Toxicology

385

106

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Sodium selenite (Na 2 SeO 3 ) is the selenium form used in the composition of dietary supplements, and diphenyl diselenide (PhSe) 2 is an important intermediate in organic synthesis, which increases the risk of human exposure to this chemical in the workplace. These compounds have been reported to inhibit the cerebral and hepatic aminolevulinic acid dehydratase (ALA-D) in vitro, and now we show that ascorbic acid can reverse some alterations caused by in vivo selenium exposure, but not ALA-D inhibition. The effect of Na 2 SeO 3 or (PhSe) 2 and ascorbic acid on selenium distribution, total non-protein thiol, ascorbic acid content (liver and brain) and haemoglobin was also examined. Mice were exposed to 250 mmol/kg (PhSe) 2 , or 18.75 mmol/kg Na 2 SeO 3 subcutaneously, and to ascorbic acid, twice a day, 1 mmol/kg intraperitonially, for 10 days. Hepatic ALA-D of mice treated with (PhSe) 2 was inhibited about 58% and similar results were observed in the animals that received ascorbic acid supplementation (PϽ0.01, for (PhSe) 2 -treated and (PhSe) 2 πascorbic acid-treated mice). The haemoglobin content decreased after treatment with (PhSe) 2 (PϽ0.01). However, the haemoglobin content of the (PhSe) 2 πascorbic acid group was significantly higher than in the (PhSe) 2 -treated mice (PϽ0.05), and similar to control (PϾ0.10). Ascorbic acid treatment decreased significantly the hepatic and cerebral deposition of Se in (PhSe) 2 -exposed mice (PϽ0.01). Hepatic non-protein thiol content was not changed by treatment with (PhSe) 2 , ascorbic acid or (PhSe) 2 πascorbic acid. Hepatic content of ascorbic acid was twice that in mice that received (PhSe) 2 , independent of ascorbic acid treatment (PϽ0.001). The results of this study suggest that vitamin C may have a protective role in organodiselenide intoxication.

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“…However, selectivity of allyl derivatives towards SE is low. There are several studies demonstrating that they interact with many other proteins (Hanther , 1968 ;Bjornstedt et al , 1996 ;Barbosa et al , 1998 ;Park et al , 2000 ). Moreover, allyl compounds cross through the blood-brain barrier and inhibit SE in Schwann cells blocking myelin formation, leading as a consequence to peripheral segmental demyelination and paralysis (Wagner -Recio et al, 1991 ;Ammar and Couri , 1992 ;Stowe et al , 1992 ).…”

Section: Anticholesterolemic Agentsmentioning

confidence: 99%

Squalene monooxygenase – a target for hypercholesterolemic therapy

Belter¹,

Skupińska²,

Giel-Pietraszuk

et al. 2011

BCHM

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Squalene monooxygenase catalyzes the epoxidation of C-C double bond of squalene to yield 2,3-oxidosqualene, the key step of sterol biosynthesis pathways in eukaryotes. Sterols are essential compounds of these organisms and squalene epoxidation is an important regulatory point in their synthesis. Squalene monooxygenase downregulation in vertebrates and fungi decreases synthesis of cholesterol and ergosterol, respectively, which makes squalene monooxygenase a potent and attractive target of hypercholesterolemia and antifungal therapies. Currently some fungal squalene monooxygenase inhibitors (terbinafi ne, naftifi ne, butenafi ne) are in clinical use, whereas mammalian enzymes ' inhibitors are still under investigation. Research on new squalene monooxygenase inhibitors is important due to the prevalence of hypercholesterolemia and the lack of both suffi cient and safe remedies. In this paper we (i) review data on activity and the structure of squalene monooxygenase, (ii) present its inhibitors, (iii) compare current strategies of lowering cholesterol level in blood with some of the most promising strategies, (iv) underline advantages of squalene monooxygenase as a target for hypercholesterolemia therapy, and (v) discuss safety concerns about hypercholesterolemia therapy based on inhibition of cellular cholesterol biosynthesis and potential usage of squalene monooxygenase inhibitors in clinical practice. After many years of use of statins there is some clinical evidence for their adverse effects and only partial effectiveness. Currently they are drugs of choice but are used with many restrictions, especially in case of children, elderly patients and women of childbearing potential. Certainly, for the next few years, statins will continue to be a suitable tool for cost-effective cardiovascular prevention; however research on new hypolipidemic drugs is highly desirable. We suggest that squalene monooxygenase inhibitors could become the hypocholesterolemic agents of the future.

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Selenotrisulfides. Formation by the reaction of thiols with selenious acid

Cited by 348 publications

References 16 publications

Synthesis and characterization of selenotrisulfide-derivatives of lipoic acid and lipoamide

Synthesis and characterization of selenotrisulfide-derivatives of lipoic acid and lipoamide

Diphenyl Diselenide and Ascorbic Acid Changes Deposition of Selenium and Ascorbic Acid in Liver and Brain of Mice

Squalene monooxygenase – a target for hypercholesterolemic therapy

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