The Metabolic State of Thiosulphate

Szczepkowski, T; Skarzynski, B; M, Weber

doi:10.1038/1891007a0

Cited by 21 publications

(11 citation statements)

References 2 publications

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“…The vast proportion of TS cleared by nonrenal mechanisms appears to be metabolized to sulfate (4,29,38) possibly predominantly in the liver but also in other tissues (39). TS is considered to be the principal, rapidly disappearing precursor of sulfate in mammalians (40). Thus, our study suggests that the TS metabolism is unaltered in patients with chronic renal failure.…”

Section: Discussionmentioning

confidence: 63%

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Farese¹,

Stauffer²,

Kalicki³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet.Design, setting, participants, & measurements STS was given intravenously to 10 hemodialysis patients onand off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. ResultsIn volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 Ϯ 1.82 versus 7.1 Ϯ 2.7 mol/L. Renal clearance was high in volunteers (1.86 Ϯ 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 Ϯ 0.32 ml/min per kg) than in anuric patients (2.04 Ϯ 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 Ϯ 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). ConclusionsGiven the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS.

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Section: Discussionmentioning

confidence: 63%

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Farese¹,

Stauffer²,

Kalicki³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Koj et al (1967) and Szczepkowski et al (1961) performed elegant experiments in the 1960s to demonstrate that thiosulfate plays a central role in sulfide oxidation by animal tissues. More recent work elucidated the details of thiosulfate formation from sulfide.…”

Section: Cysteine Undergoes Desulfuration To Hydrogen Sulfide (H2s) Omentioning

confidence: 99%

Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

Stipanuk

Ueki

2010

J of Inher Metab Disea

402

294

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Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions.

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“…Studies with rat liver mitochondria (Wainer, 1964) and the perfused rat liver (Simpson & Freedland, 1975) suggested that cysteine was metabolized primarily by cysteinesulphinateindependent pathways, because addition of unlabelled cysteinesulphinate had relatively little effect on metabolism of radiolabelled cysteine to sulphate or glucose. Furthermore, sulphide was a product of cysteine catabolism in homogenate systems (Stipanuk & Beck, 1982), and thiosulphate, which may be formed from sulphane sulphur (Koj et al, 1967), appeared to be a normal intermediate in the production of sulphate from cysteine in the intact rat (Szczepkowski et al, 1961). No significant production of reduced sulphur should occur via the cysteinesulphinate pathway, because the sulphur of cysteinesulphinate is already oxidized and is either released as SO2 (after transamination of cysteinesulphinate to 3-sulphinylpyruvate) or retained in taurine.…”

Section: Introductionmentioning

confidence: 98%

Metabolism of cysteine in rat hepatocytes. Evidence for cysteinesulphinate-independent pathways

Drake

Rosa

Stipanuk

1987

Biochemical Journal

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The metabolism of cysteine and cysteinesulphinate was studied in freshly isolated rat hepatocytes. Over 80O% of the 14CO2 formed from [1-14C]cysteinesulphinate could be accounted for by production of hypotaurine plus taurine in incubations of rat hepatocytes with either 1 mm-or 25 mM-cysteinesulphinate. In similar incubations with 1 mm-or 25 mM-cysteine, less than 10% of 14CO2 evolution from [1-14C]cysteine could be accounted for by production of hypotaurine plus taurine. In incubations with cysteine, but not with cysteinesulphinate, the production of urea and ammonia was substantially increased above that observed in incubations without substrate. Addition of unlabelled cysteinesulphinate did not affect 14C02 production from [1-14C]cysteine. Addition of 2-oxoglutarate resulted in a marked increase in cysteinesulphinate catabolism via the transamination pathway, but addition of neither 2-oxoglutarate nor pyruvate to the incubation system had any effect on cysteine catabolism. Inhibition of cystathionase with propargylglycine decreased 14CO2 production from [1-14C]cysteine about 50% and markedly decreased production ofammonia plus urea N; cysteinesulphinate catabolism was not affected. These data suggest that a substantial proportion of cysteine is catabolized by cysteinesulphinate-independent pathways in the rat hepatocyte and, furthermore, that cleavage of cyst(e)ine by cystathionase may be an important physiological pathway for cysteine catabolism in rat liver.

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The Metabolic State of Thiosulphate

Cited by 21 publications

References 2 publications

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

Metabolism of cysteine in rat hepatocytes. Evidence for cysteinesulphinate-independent pathways

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