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Free Radical Biology & Medicine Nov 2020Disulfide bonds are a key determinant of protein structure and function, and highly conserved across proteomes. They are particularly abundant in extracellular proteins,...
Disulfide bonds are a key determinant of protein structure and function, and highly conserved across proteomes. They are particularly abundant in extracellular proteins, including those with critical structural, ligand binding or receptor function. We demonstrate that oxidation of protein disulfides induces polymerization, and results in oxygen incorporation into the former disulfide via thiosulfinate generation. These intermediates, which have half-lives of several hours in vitro, undergo secondary reactions that cleave the disulfide bond, by irreversible hydrolysis to sulfinic and sulfonic acids, or reaction with thiols in a process that yields thiolated proteins (e.g. glutathionylated species in the case of reaction with glutathione). The adducts have been characterized by mass spectrometry (as ions corresponding to the addition of 306 and 712 Da for addition of one and two glutathione molecules, respectively) and immunoblotting. These modifications can be induced by multiple biologically-important oxidants, including HOCl, ONOOH, and HO, and on multiple proteins, demonstrating that this is a common disulfide modification pathway. Addition of glutathione to give glutathionylated proteins, can be reversed by reducing systems (e.g. tris(2-carboxyethyl)phosphine), but this does not repair the original disulfide bond. Exposure of human plasma to these modifying agents increases protein glutathionylation, demonstrating potential in vivo relevance. Overall these data provide evidence for a novel and facile route to glutathionylated proteins involving initial oxidation of a disulfide to a thiosulfinate followed by rapid reaction with GSH ('oxidant-mediated thiol-disulfide exchange'). These data elucidate a novel pathway for protein glutathionylation that may have significant implications for redox biology and cell signaling.
Topics: Disulfides; Glutathione; Glutathione Disulfide; Humans; Hydrogen Peroxide; Oxidants; Oxidation-Reduction; Sulfhydryl Compounds
PubMed: 32877736
DOI: 10.1016/j.freeradbiomed.2020.08.018 -
Food Chemistry Apr 2017During oxidation, the hydroxyl groups of starch molecules are first oxidized to carbonyl groups, then to carboxyl groups. The contents of the carbonyl and carboxyl... (Review)
Review
During oxidation, the hydroxyl groups of starch molecules are first oxidized to carbonyl groups, then to carboxyl groups. The contents of the carbonyl and carboxyl groups in a starch molecule therefore indicate the extent of starch oxidation. The mechanisms of starch oxidation with different oxidizing agents, including sodium hypochlorite, hydrogen peroxide, ozone and sodium periodate, are described in this review. The effects of these oxidizing agents on the molecular, physicochemical, thermal, pasting and morphological properties of starch are described as well. In addition, the main industrial applications of oxidized starches are presented. The present review is important for understanding the effects of oxidation on starch properties, and this information may facilitate the development of novel oxidized starches for both food and non-food applications.
Topics: Hydrogen Peroxide; Molecular Structure; Oxidants; Oxidation-Reduction; Ozone; Periodic Acid; Sodium Hypochlorite; Starch
PubMed: 27979128
DOI: 10.1016/j.foodchem.2016.10.138 -
Doklady. Biochemistry and Biophysics Nov 2021Plasminogen is a zymogenic form of plasmin, an enzyme that plays a fundamental role in the dissolution of fibrin clots as well as in many other physiological processes....
Plasminogen is a zymogenic form of plasmin, an enzyme that plays a fundamental role in the dissolution of fibrin clots as well as in many other physiological processes. For the first time, by the method of gas chromatography-mass spectrometry, post-translational modifications in the primary structure of plasminogen treated with physiologically relevant amounts of hydrogen peroxide were identified. It was found that methionine and tryptophan residues located in different structural regions of plasminogen served as targets of the oxidant. Plasminogen oxidation caused a dose-dependent effect in decreasing the fibrinogenolytic activity of plasmin evidenced by the formation of fibrinogen degradation products. The possible antioxidant role of methionines in the oxidative modification of plasminogen is discussed.
Topics: Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Oxidants; Peroxides; Plasminogen
PubMed: 34966964
DOI: 10.1134/S1607672921060053 -
The Journal of Biological Chemistry Oct 2019The free radical nitric oxide (NO) exerts biological effects through the direct and reversible interaction with specific targets ( soluble guanylate cyclase) or through... (Review)
Review
The free radical nitric oxide (NO) exerts biological effects through the direct and reversible interaction with specific targets ( soluble guanylate cyclase) or through the generation of secondary species, many of which can oxidize, nitrosate or nitrate biomolecules. The NO-derived reactive species are typically short-lived, and their preferential fates depend on kinetic and compartmentalization aspects. Their detection and quantification are technically challenging. In general, the strategies employed are based either on the detection of relatively stable end products or on the use of synthetic probes, and they are not always selective for a particular species. In this study, we describe the biologically relevant characteristics of the reactive species formed downstream from NO, and we discuss the approaches currently available for the analysis of NO, nitrogen dioxide (NO), dinitrogen trioxide (NO), nitroxyl (HNO), and peroxynitrite (ONOO/ONOOH), as well as peroxynitrite-derived hydroxyl (HO) and carbonate anion (CO) radicals. We also discuss the biological origins of and analytical tools for detecting nitrite (NO), nitrate (NO), nitrosyl-metal complexes, -nitrosothiols, and 3-nitrotyrosine. Moreover, we highlight state-of-the-art methods, alert readers to caveats of widely used techniques, and encourage retirement of approaches that have been supplanted by more reliable and selective tools for detecting and measuring NO-derived oxidants. We emphasize that the use of appropriate analytical methods needs to be strongly grounded in a chemical and biochemical understanding of the species and mechanistic pathways involved.
Topics: Free Radicals; Humans; Hydroxyl Radical; Nitrates; Nitric Oxide; Oxidants; Oxidation-Reduction; Peroxynitrous Acid; Reactive Nitrogen Species; Systems Biology
PubMed: 31409645
DOI: 10.1074/jbc.REV119.006136 -
F1000Research 2019Hypochlorous acid (HOCl; bleach) is a powerful weapon used by our immune system to eliminate invading bacteria. Yet the way HOCl actually kills bacteria and how they... (Review)
Review
Hypochlorous acid (HOCl; bleach) is a powerful weapon used by our immune system to eliminate invading bacteria. Yet the way HOCl actually kills bacteria and how they defend themselves from its oxidative action have only started to be uncovered. As this molecule induces both protein oxidation and aggregation, bacteria need concerted efforts of chaperones and antioxidants to maintain proteostasis during stress. Recent advances in the field identified several stress-activated chaperones, like Hsp33, RidA, and CnoX, which display unique structural features and play a central role in protecting the bacterial proteome during HOCl stress.
Topics: Bacteria; Bacterial Infections; Bacterial Proteins; Humans; Hypochlorous Acid; Molecular Chaperones; Oxidants; Oxidation-Reduction; Proteolysis; Stress, Physiological
PubMed: 31583082
DOI: 10.12688/f1000research.19517.1 -
Accounts of Chemical Research Feb 2015CONSPECTUS: One of the biggest challenges for humanity in the 21st century is easy access to purified and potable water. The presence of pathogens and toxins in water... (Review)
Review
CONSPECTUS: One of the biggest challenges for humanity in the 21st century is easy access to purified and potable water. The presence of pathogens and toxins in water causes more than two million deaths annually, mostly among children under the age of five. Identifying and deploying effective and sustainable water treatment technologies is critical to meet the urgent need for clean water globally. Among the various agents used in the purification and treatment of water, iron-based materials have garnered particular attention in view of their special attributes such as their earth-abundant and environmentally friendly nature. In recent years, higher-valent tetraoxy iron(VI) (Fe(VI)O4(2-), Fe(VI)), commonly termed, ferrate, is being explored for a broad portfolio of applications, including a greener oxidant in synthetic organic transformations, a water oxidation catalyst, and an efficient agent for abatement of pollutants in water. The use of Fe(VI) as an oxidant/disinfectant and further utilization of the ensuing iron(III) oxides/hydroxide as coagulants are other additional attributes of ferrate for water treatment. This multimodal action and environmentally benign character of Fe(VI) are key advantages over other commonly used oxidants (e.g., chlorine, chlorine dioxide, permanganate, hydrogen peroxide, and ozone). This Account discusses current state-of-the-art applications of Fe(VI) and the associated unique chemistry of these high-valence states of iron. The main focus centers around the description and salient properties of ferrate species involving various electron transfer and oxygen-atom transfer pathways in terms of presently accepted mechanisms. The mechanisms derive the number of electron equivalents per Fe(VI) (i.e., oxidation capacity) in treating various contaminants. The role of pH in the kinetics of the reactions and in determining the removal efficiency of pollutants is highlighted; the rates of competing reactions of Fe(VI) with itself, water, and the contaminants, which are highly pH dependent, determine the optimum pH range of maximum efficacy. The main emphasis of this account is placed on cases where various modes of ferrate action are utilized, including the treatment of nitrogen- and sulfur-containing waste products, antibiotics, viruses, bacteria, arsenic, and heavy metals. For example, the oxidative degradation of N- and S-bearing contaminants by Fe(VI) yields either Fe(II) or Fe(III) via the intermediacy of Fe(IV) and Fe(V) species, respectively (e.g., Fe(VI) → Fe(IV) → Fe(II) and Fe(VI) → Fe(V) → Fe(III)). Oxidative transformations of antibiotics such as trimethoprim by Fe(VI) generate products with no residual antibiotic activity. Disinfection and inactivation of bacteria and viruses can easily be achieved by Fe(VI). Advanced applications involve the use of ferrate for the degradation of cyanobacteria and microcystin originating from algal blooms and for covalently embedding arsenic and heavy metals into the structure of formed magnetic iron(III) oxides, therefore preventing their leaching. Applications of state-of-the-art analytical techniques, namely, in situ Mössbauer spectroscopy, rapid-freeze electron paramagnetic resonance, nuclear forward scattering of synchrotron radiation, and mass spectrometry will enhance the mechanistic understanding of ferrate species. This will make it possible to unlock the true potential of ferrates for degrading emerging toxins and pollutants, and in the sustainable production and use of nanomaterials in an energy-conserving environment.
Topics: Green Chemistry Technology; Iron; Oxidants; Water Microbiology; Water Pollutants, Chemical; Water Purification
PubMed: 25668700
DOI: 10.1021/ar5004219 -
Free Radical Biology & Medicine Sep 2022The mechanisms underlying the inactivation of Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase (G6PDH) induced by peroxyl radicals (ROO) and peroxynitrite...
Role of amino acid oxidation and protein unfolding in peroxyl radical and peroxynitrite-induced inactivation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides.
The mechanisms underlying the inactivation of Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase (G6PDH) induced by peroxyl radicals (ROO) and peroxynitrite (ONOO), were explored. G6PDH was incubated with AAPH (2,2' -azobis(2-methylpropionamidine)dihydrochloride), used as ROO source, and ONOO. Enzymatic activity was assessed by NADPH generation, while oxidative modifications were analyzed by gel electrophoresis and liquid chromatography (LC) with fluorescence and mass detection. Changes in protein conformation were studied by circular dichroism (CD) and binding of the fluorescent dye ANS (1-anilinonaphthalene-8-sulfonic acid). Incubation of G6PDH (54.4 μM) with 60 mM AAPH showed an initial phase without significant changes in enzymatic activity, followed by a secondary time-dependent continuous decrease in activity to ∼59% of the initial level after 90 min. ONOO induced a significant and concentration-dependent loss of G6PDH activity with ∼46% of the initial activity lost on treatment with 1.5 mM ONOO. CD and ANS fluorescence indicated changes in G6PDH secondary structure with exposure of hydrophobic sites on exposure to ROO, but not ONOO. LC-MS analysis provided evidence for ONOO-mediated oxidation of Tyr, Met and Trp residues, with damage to critical Met and Tyr residues underlying enzyme inactivation, but without effects on the native (dimeric) state of the protein. In contrast, studies using chloramine T, a specific oxidant of Met, provided evidence that oxidation of specific Met and Trp residues and concomitant protein unfolding, loss of dimer structure and protein aggregation are involved in G6PDH inactivation by ROO. These two oxidant systems therefore have markedly different effects on G6PDH structure and activity.
Topics: Amino Acids; Glucosephosphate Dehydrogenase; Leuconostoc mesenteroides; Oxidants; Oxidation-Reduction; Peroxides; Peroxynitrous Acid; Protein Unfolding
PubMed: 35987422
DOI: 10.1016/j.freeradbiomed.2022.08.010 -
The Journal of Organic Chemistry Mar 2022The synthesis of carbonyl derivatives from renewable feedstocks, by direct oxidation/functionalization of activated and unactivated C(sp)-H bonds under a controlled and...
The synthesis of carbonyl derivatives from renewable feedstocks, by direct oxidation/functionalization of activated and unactivated C(sp)-H bonds under a controlled and predictably selective fashion, especially in late stages, remains a formidable challenge. Herein, for the first time, cost-effective and widely applicable protocols for controlled and predictably selective oxidation of petroleum waste and feedstock ingredients like methyl-/alkylarenes to corresponding value-added carbonyls have been developed, using a surfactant-based oxodiperoxo molybdenum catalyst in water. The methodologies use hydrogen peroxide (HO) as an environmentally benign green oxidant, and the reactions preclude the need of any external base, additive, or cocatalyst and can be operated under mild eco-friendly conditions. The developed protocols show a wide substrate scope and eminent functional group tolerance, especially oxidation-liable and reactive boronic acid groups. Upscaled multigram synthesis of complex steroid molecules by late-stage oxidation proves the robustness and practical utility of the current protocol since it employs an inexpensive recyclable catalyst and an easily available oxidant. A plausible mechanism has been proposed with the help of few controlled experiments and kinetic and computational studies.
Topics: Catalysis; Hydrogen Peroxide; Molybdenum; Oxidants; Water
PubMed: 35098716
DOI: 10.1021/acs.joc.1c02855 -
Advances in Experimental Medicine and... 2015Cytochrome P450 (P450 or CYP) catalysis involves the oxygenation of organic compounds via a series of catalytic intermediates, namely, the ferric-peroxo,... (Review)
Review
Cytochrome P450 (P450 or CYP) catalysis involves the oxygenation of organic compounds via a series of catalytic intermediates, namely, the ferric-peroxo, ferric-hydroperoxo, Compound I (Cpd I) and FeIII-(H2O2) intermediates. Now that the structures of P450 enzymes have been well established, a major focus of current research in the P450 area has been unraveling the intimate details and activities of these reactive intermediates. The general consensus is that the Cpd I intermediate is the most reactive species in the reaction cycle, especially when the reaction involves hydrocarbon hydroxylation. Cpd I has recently been characterized experimentally. Other than Cpd I, there is a multitude of evidence, both experimental as well as theoretical, supporting the involvement of other intermediates in various types of oxidation reactions. The involvement of these multiple oxidants has been experimentally demonstrated using P450 active-site mutants in epoxidation, heteroatom oxidation and dealkylation reactions. In this chapter, we will review the P450 reaction cycle and each of the reactive intermediates to discuss their role in oxidation reactions.
Topics: Animals; Catalysis; Cytochrome P-450 Enzyme System; Humans; Hydrogen Peroxide; Iron; Oxidants; Oxidation-Reduction
PubMed: 26002731
DOI: 10.1007/978-3-319-16009-2_2 -
Journal of Environmental Management Nov 2023Disinfection and decontamination of water by application of oxidisers is an essential treatment step across numerous industrial sectors including potable supply and... (Review)
Review
Disinfection and decontamination of water by application of oxidisers is an essential treatment step across numerous industrial sectors including potable supply and industry waste management, however, could be greatly enhanced if operated as advanced oxidation processes (AOPs). AOPs destroy contaminants including pathogens by uniquely harnessing radical chemistry. Despite AOPs offer great practical opportunities, no reviews to date have highlighted the critical AOP virtues that facilitate AOPs' scale up under growing industrial demand. Hence, this review analyses the critical AOP parameters such as oxidant conversion efficiency, batch mode vs continuous-flow systems, location of radical production, radical delivery by advanced micro-/mesoporous structures and AOP process costs to assist the translation of progressing developments of AOPs into their large-scale applications. Additionally, the state of the art is analysed for various AOP inducing radical/oxidiser measurement techniques and their half-lives with a view to identify radicals/oxidisers that are suitable for in-situ production. It is concluded that radicals with short half-lives such as hydroxyl (10 μsec) and sulfate (30-40 μsec) need to be produced in-situ via continuous-flow reactors for their effective transport and dosing. Meanwhile, radicals/oxidisers with longer half-lives such as ozone (7-10 min), hydrogen peroxide (stable for several hours), and hypochlorous acid (10 min -17 h) need to be applied through batch reactor systems due to their relatively longer stability during transportation and dosing. Complex and costly synthesis as well as cytotoxicity of many micro-/mesoporous structures limit their use in scaling up AOPs, particularly to immobilising and delivering the short-lived hydroxyl and sulfate radicals to their point of applications. Overall, radical delivery using safe and advanced biocompatible micro-/mesoporous structures, radical conversion efficiency using advanced reactor design and portability of AOPs are priority areas of development for scaling up to industry.
Topics: Oxidation-Reduction; Oxidants; Disinfection; Hydrogen Peroxide; Hydroxyl Radical; Sulfates
PubMed: 37651902
DOI: 10.1016/j.jenvman.2023.118861