The Roles of Glutathione, Thioltransferase, and Glutathione Reductase in the Scission of Sulfur-Sulfur Bonds

Mannervik, Bengt; Axelsson, Kent

doi:10.1007/978-3-642-67132-6_18

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…Because also GSSG is at a low level in plant material under normal conditions (42), GSSO 3 2Ϫ is not expected to accumulate to high concentrations. Should it be formed, however, it can either be reduced to GSH and SO 3 2Ϫ by glutathione reductase (43) or react nonenzymatically with GSH to form GSSG and SO 3 2Ϫ (3). The yellow color of the purified APS reductase brings to mind the molecular structure of dissimilatory APS reductases which contain FAD and iron-sulfur clusters (3).…”

Section: Discussionmentioning

confidence: 99%

Adenosine 5′-Phosphosulfate Sulfotransferase and Adenosine 5′-Phosphosulfate Reductase Are Identical Enzymes

Suter¹,

Ballmoos²,

Kopriva³

et al. 2000

Journal of Biological Chemistry

103

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Adenosine 5-phosphosulfate (APS) sulfotransferase and APS reductase have been described as key enzymes of assimilatory sulfate reduction of plants catalyzing the reduction of APS to bound and free sulfite, respectively. APS sulfotransferase was purified to homogeneity from Lemna minor and compared with APS reductase previously obtained by functional complementation of a mutant strain of Escherichia coli with an Arabidopsis thaliana cDNA library. APS sulfotransferase was a homodimer with a monomer M r of 43,000. Its amino acid sequence was 73% identical with APS reductase. APS sulfotransferase purified from Lemna as well as the recombinant enzyme were yellow proteins, indicating the presence of a cofactor. Like recombinant APS reductase, recombinant APS sulfotransferase used APS (K m ‫؍‬ 6.5 M) and not adenosine 3-phosphate 5-phosphosulfate as sulfonyl donor. The V max of recombinant Lemna APS sulfotransferase (40 mol min ؊1 mg protein ؊1 ) was about 10 times higher than the previously published V max of APS reductase. The product of APS sulfotransferase from APS and GSH was almost exclusively SO 3 2؊ . Bound sulfite in the form of S-sulfoglutathione was only appreciably formed when oxidized glutathione was added to the incubation mixture. Because SO 3 2؊ was the first reaction product of APS sulfotransferase, this enzyme should be renamed APS reductase.Higher plants and many microorganisms growing with sulfate as sulfur source reduce it to the level of sulfide for the synthesis of cysteine, methionine, coenzymes, and iron-sulfur clusters of enzymes (1-5). The reaction sequence from sulfate to sulfide is called assimilatory sulfate reduction as opposed to dissimilatory sulfate reduction, which occurs in certain anaerobic organisms such as Desulfovibrio and Desulfotomaculum, where sulfate functions as an electron acceptor during oxidation of organic substrates and where reduced forms of sulfur are excreted into the surroundings (3).The first step of assimilatory sulfate reduction is an activation of sulfate catalyzed by ATP sulfurylase (EC 2.7.7.4). The adenosine 5Ј-phosphosulfate (APS) 1 is the substrate for APS kinase (EC 2.7.1.2.5), which forms adenosine 3Ј-phosphate 5Ј-phosphosulfate (PAPS) in a second activation step (1-5). The subsequent reduction sequence starting from PAPS is well established in bacteria (4) and fungi (6), where a PAPS reductase (EC 1.8.99) reacts first with reduced thioredoxin then with PAPS to form SO 3 2Ϫ , oxidized thioredoxin, and adenosine 3Ј-phosphate 5Ј-phosphate (PAP) (4, 7, 8). The SO 3 2Ϫ is reduced to sulfide by sulfite reductase (EC 1.8.7.1). Sulfide is finally incorporated into O-acetyl-L-serine via O-acetyl-L-serine thiollyase (EC 4.2.99.8), thus forming cysteine (1-4). All these enzymes were detected in plants (1-5, 7-11), indicating that the identical reaction sequence is operative. In two early reports it was demonstrated, however, that plants and algae use APS rather than PAPS as sulfonyl donor for the first reduction step (12, 13). APS-dependent enzymes were partially p...

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Section: Discussionmentioning

confidence: 99%

Adenosine 5′-Phosphosulfate Sulfotransferase and Adenosine 5′-Phosphosulfate Reductase Are Identical Enzymes

Suter¹,

Ballmoos²,

Kopriva³

et al. 2000

Journal of Biological Chemistry

103

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“…Finally, the last class of synthetic polymer, originally termed poly amido amines containing multiple disulfide linkages, here will be referred to as poly(disulfide amines) that contain a sulfide bond in their backbone (Figure 2F). 98 The sulfide bond allows for high biocompatibility, as it can be broken down by glutathione, a biomolecule that is prevalent in the cytoplasm of most cells 99 …”

Section: Recent Progress and Developmentmentioning

confidence: 99%

“…98 The sulfide bond allows for high biocompatibility, as it can be broken down by glutathione, a biomolecule that is prevalent in the cytoplasm of most cells. 99 Zhang et al developed a poly(disulfide amine), which they referred to as poly((N, N 0 -bis(acryloyl)cystamine-co-ethylenediamine)g-Nω-p-tosyl-L-arginine) (PBR) polycations. 78 They synthesized this polymer by Michael addition producing the poly(disulfide amine) followed by the introduction of arginine groups.…”

Section: Poly(disulfide Amines)mentioning

confidence: 99%

Trends in the synthetic polymer delivery of RNA

Friesen,

Blakney

2024

The Journal of Gene Medicine

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Ribonucleic acid (RNA) has emerged as one of the most promising therapeutic payloads in the field of gene therapy. There are many unique types of RNA that allow for a range of applications including vaccination, protein replacement therapy, autoimmune disease treatment, gene knockdown and gene editing. However, RNA triggers the host immune system, is vulnerable to degradation and has a low proclivity to enter cells spontaneously. Therefore, a delivery vehicle is required to facilitate the protection and uptake of RNA therapeutics into the desired host cells. Lipid nanoparticles have emerged as one of the only clinically approved vehicles for genetic payloads, including in the COVID‐19 messenger RNA vaccines. While lipid nanoparticles have distinct advantages, they also have drawbacks, including strong immune stimulation, complex manufacturing and formulation heterogeneity. In contrast, synthetic polymers are a widely studied group of gene delivery vehicles and boast distinct advantages, including biocompatibility, tunability, inexpensiveness, simple formulation and ease of modification. Some classes of polymers enhance efficient transfection efficiency, and lead to lower stimulation of the host immune system, making them more viable candidates for non‐vaccine‐related applications of RNA medicines. This review aims to identify the most promising classes of synthetic polymers, summarize recent research aimed at moving them into the clinic and postulate the future steps required for unlocking their full potential.

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