Identification of plasma proteins containing sulfite-reactive disulfide bonds

Gregory, R.E.; Gunnison, Albert F.

doi:10.1016/0009-2797(84)90052-8

Cited by 12 publications

(6 citation statements)

References 26 publications

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“…This argument is undermined by the low concentration of protein disulfides in the reducing milieu of the cell and the high intracellular concentration of reduced glutathione, which readily reacts with S-sulfonates to release sulfite 48 . Nearly all of the protein-bound sulfite in plasma is attributable to the reaction of sulfite with a single highly reactive cysteine in albumin, which exists mainly as a mixed sulfide with low molecular weight thiols 49 . It is noteworthy that sulfite does not react with any of the 17 cystine disulfides in albumin, a protein present at very high concentration in plasma (40 mg/mL).…”

Section: Resultsmentioning

confidence: 99%

Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism

2017

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Hydrogen sulfide (HS) is an endogenously synthesized signaling molecule that is enzymatically metabolized in mitochondria. The metabolism of HS maintains optimal concentrations of the gasotransmitter and produces sulfane sulfur (S)-containing metabolites that may be functionally important in signaling. Sulfide:quinone oxidoreductase (SQOR) catalyzes the initial two-electron oxidation of HS to S using coenzyme Q as the electron acceptor in a reaction that requires a third substrate to act as the acceptor of S. We discovered that sulfite is a highly efficient acceptor and proposed that sulfite is the physiological acceptor in a reaction that produces thiosulfate, a known metabolic intermediate. This model has been challenged by others who assume that the intracellular concentration of sulfite is very low, a scenario postulated to favor reaction of SQOR with a considerably poorer acceptor, glutathione. In this study, we measured the intracellular concentration of sulfite and other metabolites in mammalian tissues. The values observed for sulfite in rat liver (9.2 μM) and heart (38 μM) are orders of magnitude higher than previously assumed. We discovered that the apparent kinetics of oxidation of HS by SQOR with glutathione as the S acceptor reflect contributions from other SQOR-catalyzed reactions, including a novel glutathione:CoQ reductase reaction. We used observed metabolite levels and steady-state kinetic parameters to simulate rates of oxidation of HS by SQOR at physiological concentrations of different S acceptors. The results show that the reaction with sulfite as the S acceptor is a major pathway in liver and heart and provide insight into the potential dynamics of HS metabolism.

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Section: Resultsmentioning

confidence: 99%

Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism

2017

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“…Sulfitolysis of disulfide bonds of intracellular glutathione, oxidized form (GSSG) was also proposed to explain the increase in glutathione, reduced form (GSH) in the medium during perfusion of liver with sulfite [33]. Following its uptake, sulfite was generally believed to react with protein disulfide bonds to form protein-S-sulfonates [36]. Thus, sulfite is normally present in human serum in a bound form [14].…”

Section: Discussionmentioning

confidence: 99%

Sulfite-mediated oxidative stress in kidney cells

Vincent

Lim

Tan

et al. 2004

Kidney International

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“…The reaction involves the nucleophilic attack of the sulfite ions on disulfide bonds in proteins (Cecil and Wake 1962). For example, S ‐sulfonation of albumin and fibronectin is well documented (Gregory and Gunnison 1984). Figure 8 shows reactions that can lead to S ‐sulfonation of TTR.…”

Section: Discussionmentioning

confidence: 99%

Identification of S‐sulfonation and S‐thiolation of a novel transthyretin Phe33Cys variant from a patient diagnosed with familial transthyretin amyloidosis

et al. 2003

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Familial transthyretin amyloidosis (ATTR) is an autosomal dominant disorder associated with a variant form of the plasma carrier protein transthyretin (TTR). Amyloid fibrils consisting of variant TTR, wild-type TTR, and TTR fragments deposit in tissues and organs. The diagnosis of ATTR relies on the identification of pathologic TTR variants in plasma of symptomatic individuals who have biopsy proven amyloid disease. Previously, we have developed a mass spectrometry-based approach, in combination with direct DNA sequence analysis, to fully identify TTR variants. Our methodology uses immunoprecipitation to isolate TTR from serum, and electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry (MS) peptide mapping to identify TTR variants and posttranslational modifications. Unambiguous identification of the amino acid substitution is performed using tandem MS (MS/MS) analysis and confirmed by direct DNA sequence analysis. The MS and MS/MS analyses also yield information about posttranslational modifications. Using this approach, we have recently identified a novel pathologic TTR variant. This variant has an amino acid substitution (Phe → Cys) at position 33. In addition, like the Cys10 present in the wild type and in this variant, the Cys33 residue was both S-sulfonated and S-thiolated (conjugated to cysteine, cysteinylglycine, and glutathione). These adducts may play a role in the TTR fibrillogenesis.

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Identification of plasma proteins containing sulfite-reactive disulfide bonds

Cited by 12 publications

References 26 publications

Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism

Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism

Sulfite-mediated oxidative stress in kidney cells

Identification of S‐sulfonation and S‐thiolation of a novel transthyretin Phe33Cys variant from a patient diagnosed with familial transthyretin amyloidosis

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