Pub Date : 2025-03-01DOI: 10.1016/j.rbc.2024.100046
Chryssostomos Chatgilialoglu , Bronisław Marciniak , Krzysztof Bobrowski
Disulfide radical anions (RSSR•−) derive both from the direct electron attachment to disulfide-containing compounds and the reaction of thiyl radicals with thiolate, being also reversible (RS• + RS− ⇆ RSSR•−). The investigation of these reactive intermediates started in 1960s by pulse radiolysis (PR) technique and electron spin resonance (ESR) spectroscopy, and more recently, their generation was studied in organic chemistry and biological mechanisms. The present review addresses a compendium on structural, chemical and spectroscopical properties of disulfide radical anions, as well as their involvement in synthetical and biological processes. Particular emphasis is given to disulfide moieties as reactive sites in proteins, and to the generation of small sulfur-centered radicals, connected to the discovery of a mechanism of tandem protein-lipid damage. Other important biologically related processes involving disulfide radical anions are treated in the review, such as: its formation from the glutathione thiyl radical GS• (GS• + GS− ⇆ GSSG•−), resulting from the antioxidant reactivity of glutathione (GSH/GS–), and the reduction of a ketone moiety by the disulfide radical anion at the active site of the enzymes ribonucleotide reductase (RNRs), the latter used for establishing a bioinspired reduction process in organic synthesis.
{"title":"Properties of disulfide radical anions and their reactions in chemistry and biology","authors":"Chryssostomos Chatgilialoglu , Bronisław Marciniak , Krzysztof Bobrowski","doi":"10.1016/j.rbc.2024.100046","DOIUrl":"10.1016/j.rbc.2024.100046","url":null,"abstract":"<div><div>Disulfide radical anions (RSSR<sup>•−</sup>) derive both from the direct electron attachment to disulfide-containing compounds and the reaction of thiyl radicals with thiolate, being also reversible (RS<sup>•</sup> + RS<sup>−</sup> ⇆ RSSR<sup>•−</sup>). The investigation of these reactive intermediates started in 1960s by pulse radiolysis (PR) technique and electron spin resonance (ESR) spectroscopy, and more recently, their generation was studied in organic chemistry and biological mechanisms. The present review addresses a compendium on structural, chemical and spectroscopical properties of disulfide radical anions, as well as their involvement in synthetical and biological processes. Particular emphasis is given to disulfide moieties as reactive sites in proteins, and to the generation of small sulfur-centered radicals, connected to the discovery of a mechanism of tandem protein-lipid damage. Other important biologically related processes involving disulfide radical anions are treated in the review, such as: its formation from the glutathione thiyl radical GS<sup>•</sup> (GS<sup>•</sup> + GS<sup>−</sup> ⇆ GSSG<sup>•−</sup>), resulting from the antioxidant reactivity of glutathione (GSH/GS<sup>–</sup>), and the reduction of a ketone moiety by the disulfide radical anion at the active site of the enzymes ribonucleotide reductase (RNRs), the latter used for establishing a bioinspired reduction process in organic synthesis.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"11 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox reactions can modulate metabolic and signaling pathways with consequences on cellular adaptation to different stimuli. The abundance and structural features of some metabolic enzymes make these targets of oxidants, including one- and two-electron oxidant molecules, altering their structure and/or function. Therefore, redox processes play an important role in physiology and pathology. In particular, the oxidative post-translational modification of the enzymes that participate in glycolysis and the pentose phosphate pathway (PPP) can modulate the carbon flux affecting synthesis of nucleotides, as well as production of adenosine triphosphate (ATP) and reducing equivalents (in the form of nicotinamide adenine dinucleotide phosphate, NADPH). Specifically, generation of NADPH, a cofactor important for cell homeostasis, is key to the management of the redox status of cells towards oxidative insults. In this review we discuss the available literature on the impact of oxidative post-translational modifications on key glycolytic and PPP enzymes with an analysis of the consequences these may have for cell metabolic adaptation. We also discuss the contributions of new experimental and in silico approaches to the redox biochemistry field, which have significantly illuminated the intricate relationship between the pathways involved in carbohydrate metabolism and how these could be regulated by redox reactions.
{"title":"Enzymes of glycolysis and the pentose phosphate pathway as targets of oxidants: Role of redox reactions on the carbohydrate catabolism","authors":"Eduardo Fuentes-Lemus , Karen Usgame , Angélica Fierro , Camilo López-Alarcón","doi":"10.1016/j.rbc.2025.100049","DOIUrl":"10.1016/j.rbc.2025.100049","url":null,"abstract":"<div><div>Redox reactions can modulate metabolic and signaling pathways with consequences on cellular adaptation to different stimuli. The abundance and structural features of some metabolic enzymes make these targets of oxidants, including one- and two-electron oxidant molecules, altering their structure and/or function. Therefore, redox processes play an important role in physiology and pathology. In particular, the oxidative post-translational modification of the enzymes that participate in glycolysis and the pentose phosphate pathway (PPP) can modulate the carbon flux affecting synthesis of nucleotides, as well as production of adenosine triphosphate (ATP) and reducing equivalents (in the form of nicotinamide adenine dinucleotide phosphate, NADPH). Specifically, generation of NADPH, a cofactor important for cell homeostasis, is key to the management of the redox status of cells towards oxidative insults. In this review we discuss the available literature on the impact of oxidative post-translational modifications on key glycolytic and PPP enzymes with an analysis of the consequences these may have for cell metabolic adaptation. We also discuss the contributions of new experimental and <em>in silico</em> approaches to the redox biochemistry field, which have significantly illuminated the intricate relationship between the pathways involved in carbohydrate metabolism and how these could be regulated by redox reactions.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"11 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-07DOI: 10.1016/j.rbc.2025.100048
Ana C. Lopez , Silvina Acosta , Mauricio Mastrogiovanni , Williams Porcal , María Magdalena Portela , Rosario Durán , Rafael Radi , Ana Denicola , Matias N. Möller
Oxidative modifications in proteins have been extensively studied and found to increase in diabetes, cardiovascular diseases, neurodegenerative diseases, and aging. Some of the most studied modifications include the nitration of tyrosine and the formation of carbonyls in proteins. Tyrosine can also be oxidized to 3-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-L-alanine (HOCHDA) by several biologically relevant systems, a product that is electrophilic and reactive to biological nucleophiles such as glutathione. Herein, we characterized the reaction of a peptide containing HOCHDA with fluorescein-tagged glutathione by HPLC and mass spectrometry. To explore the possibility that the formation of oxidation-derived electrophiles occurs in proteins, we oxidized the tyrosine-rich, small protein, ribonuclease A, by different biologically relevant oxidizing systems and used fluorescein-tagged glutathione as the nucleophilic reagent. Oxidation of ribonuclease A with singlet oxygen, known to generate HOCHDA efficiently, generated an electrophile that reacted with fluorescein-tagged glutathione and was resistant to reduction by dithiothreitol. The amount of fluorescein-glutathione attached to the protein was quantified by gel filtration HPLC. Other oxidants such as peroxyl radical (from AAPH), ferryl (from hydrogen peroxide reaction with Fe(II):EDTA), and peroxynitrite, also generated a modified protein that reacted with fluorescein-glutathione. Analysis by LC-MS/MS indicated the formation of mono-oxygenated tyrosyl residues and di-oxygenated histidyl residues after exposure of the protein to AAPH which are good candidates to be the electrophilic centers. The formation of electrophiles was a common feature in the reactions of oxidants with ribonuclease A and may constitute an underappreciated mechanism of protein oxidative modification.
{"title":"Formation of protein-derived electrophiles in ribonuclease A by biologically relevant oxidants","authors":"Ana C. Lopez , Silvina Acosta , Mauricio Mastrogiovanni , Williams Porcal , María Magdalena Portela , Rosario Durán , Rafael Radi , Ana Denicola , Matias N. Möller","doi":"10.1016/j.rbc.2025.100048","DOIUrl":"10.1016/j.rbc.2025.100048","url":null,"abstract":"<div><div>Oxidative modifications in proteins have been extensively studied and found to increase in diabetes, cardiovascular diseases, neurodegenerative diseases, and aging. Some of the most studied modifications include the nitration of tyrosine and the formation of carbonyls in proteins. Tyrosine can also be oxidized to 3-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-L-alanine (HOCHDA) by several biologically relevant systems, a product that is electrophilic and reactive to biological nucleophiles such as glutathione. Herein, we characterized the reaction of a peptide containing HOCHDA with fluorescein-tagged glutathione by HPLC and mass spectrometry. To explore the possibility that the formation of oxidation-derived electrophiles occurs in proteins, we oxidized the tyrosine-rich, small protein, ribonuclease A, by different biologically relevant oxidizing systems and used fluorescein-tagged glutathione as the nucleophilic reagent. Oxidation of ribonuclease A with singlet oxygen, known to generate HOCHDA efficiently, generated an electrophile that reacted with fluorescein-tagged glutathione and was resistant to reduction by dithiothreitol. The amount of fluorescein-glutathione attached to the protein was quantified by gel filtration HPLC. Other oxidants such as peroxyl radical (from AAPH), ferryl (from hydrogen peroxide reaction with Fe(II):EDTA), and peroxynitrite, also generated a modified protein that reacted with fluorescein-glutathione. Analysis by LC-MS/MS indicated the formation of mono-oxygenated tyrosyl residues and di-oxygenated histidyl residues after exposure of the protein to AAPH which are good candidates to be the electrophilic centers. The formation of electrophiles was a common feature in the reactions of oxidants with ribonuclease A and may constitute an underappreciated mechanism of protein oxidative modification.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"11 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.rbc.2024.100045
Michael J. Davies (Joint Editor-in-Chief), Rafael Radi (Joint Editor-in-Chief)
{"title":"Editorial: Special issue celebrating the work of Prof. Christine C. Winterbourn","authors":"Michael J. Davies (Joint Editor-in-Chief), Rafael Radi (Joint Editor-in-Chief)","doi":"10.1016/j.rbc.2024.100045","DOIUrl":"10.1016/j.rbc.2024.100045","url":null,"abstract":"","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100045"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.rbc.2024.100044
Ari Zeida, Jacek Zielonka, Madia Trujillo
{"title":"Special issue on “Peroxynitrite and Reactive Nitrogen Species” dedicated to the 25th anniversary of the nitric oxide Nobel Prize","authors":"Ari Zeida, Jacek Zielonka, Madia Trujillo","doi":"10.1016/j.rbc.2024.100044","DOIUrl":"10.1016/j.rbc.2024.100044","url":null,"abstract":"","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100044"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.rbc.2024.100043
Ann-Kathrin Weishaupt , Anna Gremme , Torben Meiners , Vera Schwantes , Karsten Sarnow , Alicia Thiel , Tanja Schwerdtle , Michael Aschner , Heiko Hayen , Julia Bornhorst
While copper (Cu) is an essential trace element for biological systems due to its redox properties, excess levels may lead to adverse effects partly due to overproduction of reactive species. Thus, a tightly regulated Cu homeostasis is crucial for health. Cu dyshomeostasis and elevated labile Cu levels are associated with oxidative stress and neurodegenerative disorders, but the underlying mechanisms have yet to be fully characterized. Here, we used Caenorhabditis elegans loss-of-function mutants of the Cu chaperone ortholog atox-1 and the Cu binding protein ortholog ceruloplasmin to model Cu dyshomeostasis, as they display a shifted ratio of total Cu towards labile Cu. We applied highly selective and sensitive techniques to quantify metabolites associated to oxidative stress with focus on mitochondrial integrity, oxidative DNA damage and neurodegeneration all in the context of a disrupted Cu homeostasis. Our novel data reveal elevated oxidative stress, compromised mitochondria displaying reduced ATP levels and cardiolipin content. Cu dyshomeostasis further induced oxidative DNA damage and impaired DNA damage response as well as neurodegeneration characterized by behavior and neurotransmitter analysis. Our study underscores the essentiality of a tightly regulated Cu homeostasis as well as mitochondrial integrity for both genomic and neuronal stability.
铜（Cu）具有氧化还原特性，是生物系统不可或缺的微量元素，但过量的铜可能会导致不良影响，部分原因是活性物质的过度产生。因此，严格调节铜的平衡对健康至关重要。铜失衡和易变铜含量升高与氧化应激和神经退行性疾病有关，但其潜在机制尚未完全定性。在这里，我们利用秀丽隐杆线虫Cu伴侣蛋白直向同源物atox-1和Cu结合蛋白直向同源物ceruloplasmin的功能缺失突变体来模拟Cu失衡，因为这些突变体显示出总Cu与游离Cu的比例偏移。我们采用了高选择性和高灵敏度的技术来量化与氧化应激相关的代谢物，重点关注线粒体完整性、氧化 DNA 损伤和神经退行性变，所有这些都是在铜平衡失调的背景下发生的。我们的新数据显示，氧化应激升高，线粒体受损，显示出 ATP 水平和心磷脂含量降低。铜平衡失调进一步诱导了氧化 DNA 损伤和 DNA 损伤反应受损，以及以行为和神经递质分析为特征的神经退行性变。我们的研究强调了严格调节的铜平衡以及线粒体完整性对基因组和神经元稳定性的重要性。
{"title":"Dysfunctional copper homeostasis in Caenorhabditis elegans affects genomic and neuronal stability","authors":"Ann-Kathrin Weishaupt , Anna Gremme , Torben Meiners , Vera Schwantes , Karsten Sarnow , Alicia Thiel , Tanja Schwerdtle , Michael Aschner , Heiko Hayen , Julia Bornhorst","doi":"10.1016/j.rbc.2024.100043","DOIUrl":"10.1016/j.rbc.2024.100043","url":null,"abstract":"<div><div>While copper (Cu) is an essential trace element for biological systems due to its redox properties, excess levels may lead to adverse effects partly due to overproduction of reactive species. Thus, a tightly regulated Cu homeostasis is crucial for health. Cu dyshomeostasis and elevated labile Cu levels are associated with oxidative stress and neurodegenerative disorders, but the underlying mechanisms have yet to be fully characterized. Here, we used <em>Caenorhabditis elegans</em> loss-of-function mutants of the Cu chaperone ortholog atox-1 and the Cu binding protein ortholog ceruloplasmin to model Cu dyshomeostasis, as they display a shifted ratio of total Cu towards labile Cu. We applied highly selective and sensitive techniques to quantify metabolites associated to oxidative stress with focus on mitochondrial integrity, oxidative DNA damage and neurodegeneration all in the context of a disrupted Cu homeostasis. Our novel data reveal elevated oxidative stress, compromised mitochondria displaying reduced ATP levels and cardiolipin content. Cu dyshomeostasis further induced oxidative DNA damage and impaired DNA damage response as well as neurodegeneration characterized by behavior and neurotransmitter analysis. Our study underscores the essentiality of a tightly regulated Cu homeostasis as well as mitochondrial integrity for both genomic and neuronal stability.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100043"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20DOI: 10.1016/j.rbc.2024.100041
Sergei V. Lymar , James K. Hurst
Many chemical and biological reactions involving peroxynitrite3 occur by unusual rate laws that are independent of the identity of the reacting partner. The true nature of these reactions and the identities of actual reactive species have been the subject of considerable debate ever since the notion that peroxynitrite is an important component of oxidative stress was first introduced in the early 1990s. We present herein a succinct historical review of this topic written from the perspective that intermediary inorganic free radicals are the causative agents in these reactions. This viewpoint provides a complete self-consistent rationalization of all verified data from multiple laboratories, whereas other explanations have been unable to do so. Recognition of the radical nature of peroxynitrite decomposition has also allowed a reassessment of the quantitative mechanism of CO2-catalyzed peroxynitrite decomposition. Detailed analyses indicate that the constant for rate-limiting formation of the putative reactive carbon dioxide adduct ()3 is actually ∼20% less than previously recognized and CO2 turnover numbers for catalysis (that is, the number of reaction cycles that CO2 undergoes before being removed as bicarbonate) are relatively large and dependent upon the [CO2]/[ONOO−] ratio in the reaction environment.
{"title":"Perceptions of peroxynitrite reactivity – Then and now","authors":"Sergei V. Lymar , James K. Hurst","doi":"10.1016/j.rbc.2024.100041","DOIUrl":"10.1016/j.rbc.2024.100041","url":null,"abstract":"<div><div>Many chemical and biological reactions involving peroxynitrite<span><span><sup>3</sup></span></span> occur by unusual rate laws that are independent of the identity of the reacting partner. The true nature of these reactions and the identities of actual reactive species have been the subject of considerable debate ever since the notion that peroxynitrite is an important component of oxidative stress was first introduced in the early 1990s. We present herein a succinct historical review of this topic written from the perspective that intermediary inorganic free radicals are the causative agents in these reactions. This viewpoint provides a complete self-consistent rationalization of all verified data from multiple laboratories, whereas other explanations have been unable to do so. Recognition of the radical nature of peroxynitrite decomposition has also allowed a reassessment of the quantitative mechanism of CO<sub>2</sub>-catalyzed peroxynitrite decomposition. Detailed analyses indicate that the constant for rate-limiting formation of the putative reactive carbon dioxide adduct (<span><math><msup><mrow><msub><mtext>ONOOCO</mtext><mn>2</mn></msub></mrow><mo>−</mo></msup></math></span>)<span><span><sup>3</sup></span></span> is actually ∼20% less than previously recognized and CO<sub>2</sub> turnover numbers for catalysis (that is, the number of reaction cycles that CO<sub>2</sub> undergoes before being removed as bicarbonate) are relatively large and dependent upon the [CO<sub>2</sub>]/[ONOO<sup>−</sup>] ratio in the reaction environment.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1016/j.rbc.2024.100040
Monika Rola , Jacek Zielonka , Renata Smulik-Izydorczyk , Jakub Pięta , Karolina Pierzchała , Adam Sikora , Radosław Michalski
Boronates react directly and stoichiometrically with peroxynitrite and hydrogen peroxide. For this reason, boronates have been widely used as peroxynitrite- and hydrogen peroxide-sensitive moieties in various donors of bioactive compounds. So far, numerous boronate-based prodrugs and theranostics have been developed, characterized, and used in biological research. Here, the kinetic aspects of their activation are discussed, and the potential benefits of modifying their original structure with a boronic or boronobenzyl moiety are described.
{"title":"Boronate-based bioactive compounds activated by peroxynitrite and hydrogen peroxide","authors":"Monika Rola , Jacek Zielonka , Renata Smulik-Izydorczyk , Jakub Pięta , Karolina Pierzchała , Adam Sikora , Radosław Michalski","doi":"10.1016/j.rbc.2024.100040","DOIUrl":"10.1016/j.rbc.2024.100040","url":null,"abstract":"<div><p>Boronates react directly and stoichiometrically with peroxynitrite and hydrogen peroxide. For this reason, boronates have been widely used as peroxynitrite- and hydrogen peroxide-sensitive moieties in various donors of bioactive compounds. So far, numerous boronate-based prodrugs and theranostics have been developed, characterized, and used in biological research. Here, the kinetic aspects of their activation are discussed, and the potential benefits of modifying their original structure with a boronic or boronobenzyl moiety are described.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100040"},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277317662400021X/pdfft?md5=c58c101adf9a9f3d95e787fad55df43b&pid=1-s2.0-S277317662400021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-08DOI: 10.1016/j.rbc.2024.100039
Madia Trujillo , Ernesto Cuevasanta , Lucía Turell , Dayana Benchoam , Gerardo Ferrer-Sueta , Ari Zeida , Celia Quijano , Sebastián Carballal , Rafael Radi , Beatriz Alvarez
Three decades of research on the biochemistry of peroxynitrite (ONOOH/ONOO−) have established that this stealthy oxidant is formed in biological systems, and that its main targets are carbon dioxide (CO2), metalloproteins and thiols (RSH). Peroxynitrous acid reacts directly with thiols (precisely, with thiolates, RS−), forming sulfenic acids (RSOH). In addition, the free radicals derived from peroxynitrite, mainly carbonate radical anion () and nitrogen dioxide () formed from the reaction of peroxynitrite anion with CO2, oxidize thiols to thiyl radicals (RS•). These two pathways are under kinetic competition. The primary products of thiol oxidation can follow different decay routes; sulfenic acids usually react with other thiols forming disulfides, while thiyl radicals can react with oxygen, with other thiols and with other reductants such as ascorbic acid. Peroxynitrite is also able to oxidize hydrogen sulfide (H2S/HS−) and persulfides (RSSH/RSS−). Among the different biological thiols, peroxiredoxins stand out as main peroxynitrite reductases due to their very high rate constants of reaction with peroxynitrite together with their abundance. Rooted in kinetic concepts, evidence is emerging for the role of peroxiredoxins in peroxynitrite detoxification, with potential implications in diseases in which peroxynitrite is involved.
三十年来对过亚硝酸（ONOOH/ONOO-）生物化学的研究表明，这种隐形氧化剂是在生物系统中形成的，其主要目标是二氧化碳（CO2）、金属蛋白和硫醇（RSH）。过硫酸会直接与硫醇（准确地说，是与硫酸盐，RS-）反应，形成亚硫酸（RSOH）。此外，过亚硝酸产生的自由基，主要是碳酸根阴离子（CO3--）和过亚硝酸阴离子与 CO2 反应生成的二氧化氮（NO2-），会将硫醇氧化为硫自由基（RS-）。这两种途径在动力学上相互竞争。硫醇氧化的主要产物可以遵循不同的衰变途径；亚硫酸通常会与其他硫醇发生反应，形成二硫化物，而硫自由基则会与氧气、其他硫醇和其他还原剂（如抗坏血酸）发生反应。亚硫酸过氧化物还能氧化硫化氢（H2S/HS-）和过硫化物（RSSH/RSS-）。在不同的生物硫醇中，过氧化还原酶因其与亚硝酸过氧化物反应的速率常数非常高且数量丰富而成为主要的亚硝酸过氧化物还原酶。基于动力学概念，有证据表明过氧化还原酶在过亚硝酸盐解毒中的作用，并对涉及过亚硝酸盐的疾病具有潜在影响。
{"title":"Reaction of peroxynitrite with thiols, hydrogen sulfide and persulfides","authors":"Madia Trujillo , Ernesto Cuevasanta , Lucía Turell , Dayana Benchoam , Gerardo Ferrer-Sueta , Ari Zeida , Celia Quijano , Sebastián Carballal , Rafael Radi , Beatriz Alvarez","doi":"10.1016/j.rbc.2024.100039","DOIUrl":"10.1016/j.rbc.2024.100039","url":null,"abstract":"<div><p>Three decades of research on the biochemistry of peroxynitrite (ONOOH/ONOO<sup>−</sup>) have established that this stealthy oxidant is formed in biological systems, and that its main targets are carbon dioxide (CO<sub>2</sub>), metalloproteins and thiols (RSH). Peroxynitrous acid reacts directly with thiols (precisely, with thiolates, RS<sup>−</sup>), forming sulfenic acids (RSOH). In addition, the free radicals derived from peroxynitrite, mainly carbonate radical anion (<span><math><msup><msub><mi>CO</mi><mn>3</mn></msub><mrow><mo>•</mo><mo>−</mo></mrow></msup></math></span>) and nitrogen dioxide (<span><math><msup><msub><mi>NO</mi><mn>2</mn></msub><mrow><mo>•</mo></mrow></msup></math></span>) formed from the reaction of peroxynitrite anion with CO<sub>2</sub>, oxidize thiols to thiyl radicals (RS<sup>•</sup>). These two pathways are under kinetic competition. The primary products of thiol oxidation can follow different decay routes; sulfenic acids usually react with other thiols forming disulfides, while thiyl radicals can react with oxygen, with other thiols and with other reductants such as ascorbic acid. Peroxynitrite is also able to oxidize hydrogen sulfide (H<sub>2</sub>S/HS<sup>−</sup>) and persulfides (RSSH/RSS<sup>−</sup>). Among the different biological thiols, peroxiredoxins stand out as main peroxynitrite reductases due to their very high rate constants of reaction with peroxynitrite together with their abundance. Rooted in kinetic concepts, evidence is emerging for the role of peroxiredoxins in peroxynitrite detoxification, with potential implications in diseases in which peroxynitrite is involved.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000208/pdfft?md5=d3ba6f796dbd6aef9cd2c5262abce81f&pid=1-s2.0-S2773176624000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-03DOI: 10.1016/j.rbc.2024.100038
Patricia L. Bounds , Willem H. Koppenol
The published syntheses of peroxynitrite from azide, nitrite, amylnitrite, hydroxylamine, nitrogen monoxide, and ammonia are discussed. With one exception, all of these syntheses yield peroxynitrite contaminated with nitrate and nitrite as well as reactants. The rate constant for the reaction of nitrogen monoxide with superoxide has been determined by pulse radiolysis and flash photolysis. In pulse radiolysis studies, the formation of the reactants may be rate-limiting and could lead to underestimation of the second-order rate constant. The conditions of flash photolysis experiments can be chosen to minimize conflict between reactant formation and the reaction half-life, thus the rate constant of 1.6 × 1010 M−1 s−1 determined by flash photolysis is preferred. The toxicity of peroxynitrite can be attributed mainly to its rapid reaction with carbon dioxide to yield the oxidizing trioxidocarbonate(•1−) and nitrogen dioxide radicals.
{"title":"Peroxynitrite: A tale of two radicals","authors":"Patricia L. Bounds , Willem H. Koppenol","doi":"10.1016/j.rbc.2024.100038","DOIUrl":"10.1016/j.rbc.2024.100038","url":null,"abstract":"<div><p>The published syntheses of peroxynitrite from azide, nitrite, amylnitrite, hydroxylamine, nitrogen monoxide, and ammonia are discussed. With one exception, all of these syntheses yield peroxynitrite contaminated with nitrate and nitrite as well as reactants. The rate constant for the reaction of nitrogen monoxide with superoxide has been determined by pulse radiolysis and flash photolysis. In pulse radiolysis studies, the formation of the reactants may be rate-limiting and could lead to underestimation of the second-order rate constant. The conditions of flash photolysis experiments can be chosen to minimize conflict between reactant formation and the reaction half-life, thus the rate constant of 1.6 × 10<sup>10</sup> M<sup>−1</sup> s<sup>−1</sup> determined by flash photolysis is preferred. The toxicity of peroxynitrite can be attributed mainly to its rapid reaction with carbon dioxide to yield the oxidizing trioxidocarbonate(•1−) and nitrogen dioxide radicals.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100038"},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000191/pdfft?md5=734775ea1595e2d19112d81fbf834ca5&pid=1-s2.0-S2773176624000191-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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