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IUBMB Life Jun 2017Iron is an essential element for almost all organisms on Earth. It is necessary for a number of crucial processes such as hemoglobin and myoglobin transport and storage... (Review)
Review
Iron is an essential element for almost all organisms on Earth. It is necessary for a number of crucial processes such as hemoglobin and myoglobin transport and storage of oxygen in mammals; electron transfer support in a variety of iron-sulfur protein or cytochrome reactions; and activation and catalysis of reactions of a wide range of substrate like alkanes, olefins, and alcohols. Living organisms adopted iron as the main metal to carry out all of these functions due to the rich coordination chemistry of its two main redox states, Fe and Fe , and because of its abundance in the Earth's crust and oceans. This paper presents an overview of the coordination chemistry of iron that makes it suitable for a large variety of functions within biological systems. Despite iron's chemical advantages, organisms were forced to manage with some drawbacks: Fe insolubility and the formation of toxic radicals, especially the hydroxyl radical. Iron chemistry within biology is an example of how organisms evolved by creating molecular machinery to overcome these difficulties and perform crucial processes with extraordinary elegance and efficiency. © 2017 IUBMB Life, 69(6):382-388, 2017.
Topics: Biological Transport; Coordination Complexes; Eukaryota; Hemoglobins; Hydroxyl Radical; Iron; Iron-Sulfur Proteins; Myoglobin; Oxidation-Reduction; Oxygen; Prokaryotic Cells
PubMed: 28150902
DOI: 10.1002/iub.1602 -
Molecules (Basel, Switzerland) Aug 2022Iron is the most abundant mineral in the human body and plays essential roles in sustaining life, such as the transport of oxygen to systemic organs. The Fenton reaction... (Review)
Review
Iron is the most abundant mineral in the human body and plays essential roles in sustaining life, such as the transport of oxygen to systemic organs. The Fenton reaction is the reaction between iron and hydrogen peroxide, generating hydroxyl radical, which is highly reactive and highly toxic to living cells. "Ferroptosis", a programmed cell death in which the Fenton reaction is closely involved, has recently received much attention. Furthermore, various applications of the Fenton reaction have been reported in the medical and nutritional fields, such as cancer treatment or sterilization. Here, this review summarizes the recent growing interest in the usefulness of iron and its biological relevance through basic and practical information of the Fenton reaction and recent reports.
Topics: Ferroptosis; Humans; Hydrogen Peroxide; Hydroxyl Radical; Iron; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 36080218
DOI: 10.3390/molecules27175451 -
Medical Gas Research 2023Intestinal bacteria can be classified into "beneficial bacteria" and "harmful bacteria." However, it is difficult to explain the mechanisms that make "beneficial... (Review)
Review
Intestinal bacteria can be classified into "beneficial bacteria" and "harmful bacteria." However, it is difficult to explain the mechanisms that make "beneficial bacteria" truly beneficial to human health. This issue can be addressed by focusing on hydrogen-producing bacteria in the intestines. Although it is widely known that molecular hydrogen can react with hydroxyl radicals, generated in the mitochondria, to protect cells from oxidative stress, the beneficial effects of hydrogen are not fully pervasive because it is not generally thought to be metabolized in vivo. In recent years, it has become clear that there is a close relationship between the amount of hydrogen produced by intestinal bacteria and various diseases, and this report discusses this relationship.
Topics: Humans; Hydrogen; Oxidative Stress; Hydroxyl Radical; Bacteria
PubMed: 36571374
DOI: 10.4103/2045-9912.344977 -
Nature Communications Jan 2022
Topics: Hydroxyl Radical; Superoxides
PubMed: 35046395
DOI: 10.1038/s41467-021-27823-2 -
Biochimica Et Biophysica Acta. Proteins... Sep 2022Fast photochemical oxidation of proteins (FPOP) is a hydroxyl radical footprinting approach whereby radicals, produced by UV laser photolysis of hydrogen peroxide,... (Review)
Review
Fast photochemical oxidation of proteins (FPOP) is a hydroxyl radical footprinting approach whereby radicals, produced by UV laser photolysis of hydrogen peroxide, induce oxidation of amino acid side-chains. Mass Spectrometry (MS) is employed to locate and quantify the resulting irreversible, covalent oxidations to use as a surrogate for side-chain solvent accessibility. Modulation of oxidation levels under different conditions allows for the characterisation of protein conformation, dynamics and binding epitopes. FPOP has been applied to structurally diverse and biopharmaceutically relevant systems from small, monomeric aggregation-prone proteins to proteome-wide analysis of whole organisms. This review evaluates the current state of FPOP, the progress needed to address data analysis bottlenecks, particularly for residue-level analysis, and highlights significant developments of the FPOP platform that have enabled its versatility and complementarity to other structural biology techniques.
Topics: Hydroxyl Radical; Mass Spectrometry; Oxidation-Reduction; Protein Conformation; Proteins
PubMed: 35933084
DOI: 10.1016/j.bbapap.2022.140829 -
Protein and Peptide Letters 2019Determination of the composition and some structural features of macromolecules can be achieved by using structural proteomics approaches coupled with mass spectrometry... (Review)
Review
BACKGROUND
Determination of the composition and some structural features of macromolecules can be achieved by using structural proteomics approaches coupled with mass spectrometry (MS). One approach is hydroxyl radical protein footprinting whereby amino-acid side chains are modified with reactive reagents to modify irreversibly a protein side chain. The outcomes, when deciphered with mass-spectrometry-based proteomics, can increase our knowledge of structure, assembly, and conformational dynamics of macromolecules in solution. Generating the hydroxyl radicals by laser irradiation, Hambly and Gross developed the approach of Fast Photochemical Oxidation of Proteins (FPOP), which labels proteins on the sub millisecond time scale and provides, with MS analysis, deeper understanding of protein structure and protein-ligand and protein- protein interactions. This review highlights the fundamentals of FPOP and provides descriptions of hydroxyl-radical and other radical and carbene generation, of the hydroxyl labeling of proteins, and of determination of protein modification sites. We also summarize some recent applications of FPOP coupled with MS in protein footprinting.
CONCLUSION
We survey results that show the capability of FPOP for qualitatively measuring protein solvent accessibility on the residue level. To make these approaches more valuable, we describe recent method developments that increase FPOP's quantitative capacity and increase the spatial protein sequence coverage. To improve FPOP further, several new labeling reagents including carbenes and other radicals have been developed. These growing improvements will allow oxidative- footprinting methods coupled with MS to play an increasingly significant role in determining the structure and dynamics of macromolecules and their assemblies.
Topics: Amyloid; Epitope Mapping; Hydroxyl Radical; Mass Spectrometry; Oxidation-Reduction; Photochemical Processes; Protein Folding; Protein Footprinting; Proteins
PubMed: 30484399
DOI: 10.2174/0929866526666181128124554 -
Environmental Science & Technology Sep 2022The photolysis of pesticides with different fluorine motifs was evaluated to quantify the formation of fluorinated products in buffered aqueous systems, advanced...
The photolysis of pesticides with different fluorine motifs was evaluated to quantify the formation of fluorinated products in buffered aqueous systems, advanced oxidation (AOP) and reduction processes (ARP), and river water. Simulated sunlight quantum yields at pH 7 were 0.0033, 0.0025, 0.0015, and 0.00012 for penoxsulam, florasulam, sulfoxaflor, and fluroxypyr, respectively. The bimolecular rate constants with hydroxyl radicals were 2 to 5.7 × 10 M s and, with sulfate radicals, 1.6 to 2.6 × 10 M s for penoxsulam, florasulam, and fluroxypyr, respectively. The rate constants of sulfoxaflor were 100-fold lower. Using quantitative F-NMR, complete fluorine mass balances were obtained. The maximum fluoride formation was 53.4 and 87.4% for penoxsulam and florasulam under ARP conditions, and 6.1 and 100% for sulfoxaflor and fluroxypyr under AOP conditions. Heteroaromatic CF and aliphatic CF groups were retained in multiple fluorinated photoproducts. Aryl F and heteroaromatic F groups were readily defluorinated to fluoride. CF and CF groups formed trifluoroacetate and difluoroacetate, and yields increased under oxidizing conditions. F-NMR chemical shifts and coupling analysis provided information on hydrogen loss on adjacent bonds or changes in chirality. Mass spectrometry results were consistent with the observed F-NMR products. These results will assist in selecting treatment processes for specific fluorine motifs and in the design of agrochemicals to reduce byproduct formation.
Topics: Fluorides; Fluorine; Hydroxyl Radical; Pesticides; Photolysis
PubMed: 35972505
DOI: 10.1021/acs.est.2c04242 -
International Journal of Molecular... Feb 2023An aromatic substrate for hydroxylation by hydroxyl radicals (OH) was investigated. The probe, '-(5-nitro-1,3-phenylene)--glutaramide, and its hydroxylated product do...
An aromatic substrate for hydroxylation by hydroxyl radicals (OH) was investigated. The probe, '-(5-nitro-1,3-phenylene)--glutaramide, and its hydroxylated product do not bind either iron(III) or iron(II), and so they do not interfere with the Fenton reaction. A spectrophotometric assay based on the hydroxylation of the substrate was developed. The synthesis and purification methods of this probe from previously published methodologies were improved upon, as well as the analytical procedure for monitoring the Fenton reaction through its use, enabling univocal and sensitive OH detection. The assay was utilised to demonstrate that the iron(III) complexes of long-chain fatty acids lack Fenton activity under biological conditions.
Topics: Hydroxyl Radical; Colorimetry; Ferric Compounds; Iron; Iron Chelating Agents; Hydroxylation; Hydrogen Peroxide
PubMed: 36835574
DOI: 10.3390/ijms24044162 -
RNA (New York, N.Y.) Aug 2003The speed at which RNA molecules decompose is a critical determinant of many biological processes, including those directly involved in the storage and expression of... (Review)
Review
The speed at which RNA molecules decompose is a critical determinant of many biological processes, including those directly involved in the storage and expression of genetic information. One mechanism for RNA cleavage involves internal phosphoester transfer, wherein the 2'-oxygen atom carries out an SN2-like nucleophilic attack on the adjacent phosphorus center (transesterification). In this article, we discuss fundamental principles of RNA transesterification and define a conceptual framework that can be used to assess the catalytic power of enzymes that cleave RNA. We deduce that certain ribozymes and deoxyribozymes, like their protein enzyme counterparts, can bring about enormous rate enhancements.
Topics: Esterification; Hydrolysis; Hydroxyl Radical; Oxygen; RNA; RNA, Catalytic
PubMed: 12869701
DOI: 10.1261/rna.5680603 -
The Journal of Physical Chemistry. B Sep 2019Class A flavin-dependent hydroxylases (FdHs) catalyze the hydroxylation of organic compounds in a site- and stereoselective manner. In stark contrast, conventional...
Class A flavin-dependent hydroxylases (FdHs) catalyze the hydroxylation of organic compounds in a site- and stereoselective manner. In stark contrast, conventional synthetic routes require environmentally hazardous reagents and give modest yields. Thus, understanding the detailed mechanism of this class of enzymes is essential to their rational manipulation for applications in green chemistry and pharmaceutical production. Both electrophilic substitution and radical intermediate mechanisms have been proposed as interpretations of FdH hydroxylation rates and optical spectra. While radical mechanistic steps are often difficult to examine directly, modern quantum chemistry calculations combined with statistical mechanical approaches can yield detailed mechanistic models providing insights that can be used to differentiate reaction pathways. In the current work, we report quantum mechanical/molecular mechanical (QM/MM) calculations on the fungal TropB enzyme that shows an alternative reaction pathway in which hydroxylation through a hydroxyl radical-coupled electron-transfer mechanism is significantly favored over electrophilic substitution. Furthermore, QM/MM calculations on several modified flavins provide a more consistent interpretation of the experimental trends in the reaction rates seen experimentally for a related enzyme, -hydroxybenzoate hydroxylase. These calculations should guide future enzyme and substrate design strategies and broaden the scope of biological spin chemistry.
Topics: 4-Hydroxybenzoate-3-Monooxygenase; Bacteria; Bacterial Proteins; Biocatalysis; Density Functional Theory; Electron Transport; Hydroxyl Radical; Hydroxylation; Molecular Dynamics Simulation
PubMed: 31532200
DOI: 10.1021/acs.jpcb.9b08178