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Summary. Activated phagocytes generate the potent oxidant hypochlorite (HOCl) via the release of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is known to react with a number of biological targets including proteins, DNA, lipids and cholesterol. Proteins are likely to be major targets for reaction with HOCl within a cell due to their abundance and high reactivity with HOCl. This review summarizes information on the rate of reaction of HOCl with proteins, the nature of the intermediates formed, the mechanisms involved in protein oxidation and the products of these reactions. The predicted targets for reaction with HOCl from kinetic modeling studies and the consequences of HOCl-induced protein oxidation are also discussed. 相似文献
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Kapiotis S Jirovetz L Hermann M Laggner H Exner M Esterbauer H Gmeiner BM 《Biochimie》2006,88(7):785-791
Hypochlorite (HOCl) attacks amino acid residues in LDL making the particle atherogenic. Tryptophan is prone to free radical reactions and modification by HOCl. We hypothesized, that free tryptophan may quench the HOCl attack therefore protecting LDL. Free tryptophan inhibits LDL apoprotein modification and lipid oxidation. Tryptophan-HOCl metabolites associate with LDL reducing its oxidizability initiated by endothelial cells, Cu(2+) and peroxyl radicals. One tryptophan-HOCl metabolite was identified as 4-methyl-carbostyril which showed antioxidative activity when present during Cu(2+) mediated lipid oxidation, but did not associate with LDL. Indole-3-acetaldehyde, a decomposition product of tryptophan chloramine (the product of the tryptophan-HOCl reaction) was found to associate with LDL increasing its resistance to oxidation. Myeloperoxidase treatment of LDL in the presence of chloride, H(2)O(2) and tryptophan protected the lipoprotein from subsequent cell-mediated oxidation. We conclude that, in vivo, the activated myeloperoxidase system can generate antioxidative metabolites from tryptophan by the reaction of hypochlorite with this essential amino acid. 相似文献
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Agnieszka Robaszkiewicz Grzegorz Bartosz 《Biochemical and biophysical research communications》2009,390(3):659-291
Peroxynitrite and hypochlorite are oxidants relevant in many pathological situations. We propose a simple spectrophotometric assay to determine antioxidant capacity against hypochlorite and peroxynitrite based on protection against Pyrogallol Red decolorization. The assay can be performed on a microplate and requires minute amounts of material. Standard antioxidants show different reactivities for both oxidants. Antioxidant capacity of blood plasma (anticoagulated with EDTA) of healthy persons was found to be 559 ± 49 μmol/l and 11.6 ± 1.2 mmol/l of ascorbic acid equivalents for peroxynitrite and hypochlorite, respectively. 相似文献
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Ramos DR García MV Canle L M Santaballa JA Furtmüller PG Obinger C 《Journal of inorganic biochemistry》2008,102(5-6):1300-1311
Myeloperoxidase (MPO) is a dominating enzyme of circulating polymorphonuclear neutrophils that catalyzes the two-electron oxidation of chloride, thereby producing the strong halogenating agent hypochlorous acid (ClO−/HOCl). In absence of MPO the tripeptide Pro-Gly-Gly reacts with HOCl faster than the amino acid taurine (2-aminoethanesulfonic acid, Tau), while the MPO-mediated chlorination shows reverse order. A comparative study of the enzymatic oxidation of both substrates at pH 4.0–6.0, varying H2O2 concentration is presented. Initial and equilibrium rates studies have been carried on, reaction rates in the latter being slower due to the chemical equilibrium between MPO-I and MPO-II–HO2. A maximum of chlorination rate is observed for Pro-Gly-Gly and Tau when [H2O2] ≈ 0.3–0.7 mM and pH ≈ 4.5–5.0. Several mechanistic possibilities are considered, the proposed one implies that chlorination takes place via two pathways. One, for bulkier substrates, involves chlorination by free HOCl outside the heme cavity; ClO− is released from the active center, diffuses away the heme cavity, and undergoes protonation to HOCl. The other implies the existence of compound I–Cl− complex (MPO-I–Cl), capable of chlorinating smaller substrates in the heme pocket. Electronic structure calculations show the size of Pro-Gly-Gly comparable to the available gap in the substrate channel, this tripeptide being unable to reach the active site, and its chlorination is only possible by free HOCl outside the enzyme. 相似文献
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Huijian Jiang Linfeng Rao Zhicheng Zhang Dhanpat Rai 《Inorganica chimica acta》2006,359(10):3237-3242
Chromium exists in nuclear waste sludges and is a problematic element in the vitrification process of high-level nuclear wastes. It is therefore necessary to treat the waste sludges to remove chromium prior to vitrification, by caustic leaching or oxidation of Cr(III) to Cr(VI). The objective of this study is to investigate the effect of oligomerization of Cr(III) on its oxidation by hypochlorite in alkaline solutions.Monomeric, dimeric and trimeric Cr(III) species in solution were separated by ion exchange. The kinetics of the oxidation of the separated species by hypochlorite in alkaline solutions was studied by UV/Vis absorption spectroscopy, and compared with the oxidation by hydrogen peroxide previously studied. Results indicate that hypochlorite can oxidize Cr(III) to Cr(VI) in alkaline solutions, but the rate of oxidation by hypochlorite is slower than that by hydrogen peroxide at the same alkalinity and concentrations of oxidants. The rate of oxidation of Cr(III) by both oxidants decreases as the concentration of sodium hydroxide is increased, but the oxidation by hypochlorite seems less affected by the degree of oligomerization of Cr(III) than that by peroxide. Compared with the oxidation by hydrogen peroxide where the major reaction pathway has an inverse order with respect to CNaOH, the oxidation by hypochlorite has a significant reaction pathway independent of [OH−]. 相似文献
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Stable markers of oxidant damage to proteins and their application in the study of human disease 总被引:7,自引:0,他引:7
The mechanisms of formation and the nature of the altered amino acid side chains formed on proteins subjected to oxidant attack are reviewed. The use of stable products of protein side chain oxidation as potential markers for assessing oxidative damage in vivo in humans is discussed. The methods developed in the authors laboratories are outlined, and the advantages and disadvantages of these techniques compared with other methodologies for assessing oxidative damage to proteins and other macromolecules. Evidence is presented to show that protein oxidation products are sensitive markers of oxidative damage, that the pattern of products detected may yield information as to the nature of the original oxidative insult, and that the levels of oxidized side-chains can, in certain circumstances, be much higher than those of other markers of oxidation such as lipid hydroperoxides. 相似文献
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Degradation of hyaluronic acid by oxidants such as HO· and HOCl/ClO− is believed to be important in the progression of rheumatoid arthritis. While reaction of hyaluronic acid with HO· has been investigated extensively, reaction with HOCl/ClO− is less well defined. Thus, little is known about the site(s) of HOCl/ClO− attack, the intermediates formed, or the mechanism(s) of polymer degradation. In this study reaction of HOCl/ClO− with amides, sugars, polysaccharides, and hyaluronic acid has been monitored by UV-visible (220–340 nm) and EPR spectroscopy. UV-visible experiments have shown that HOCl/ClO− reacts preferentially with N-acetyl groups. This reaction is believed to give rise to transient chloramide (R—NCl—C(O)—R′) species, which decompose rapidly to give radicals via either homolysis (to produce N· and Cl·) or heterolysis (one-electron reduction, to give N· and Cl−) of the N—Cl bond. The nature of the radicals formed has been investigated by EPR spin trapping. Reaction of HOCl/ClO− with hyaluronic acid, chondroitin sulphates A and C, N-acetyl sugars, and amides gave novel, carbon-centered, spin adducts, the formation of which is consistent with selective initial attack at the N-acetyl group. Thus, reaction with hyaluronic acid and chondroitin sulphate A, appears to be localized at the N-acetylglucosamine sugar rings. These carbon-centered radicals are suggested to arise from rapid rearrangement of initial nitrogen-centered radicals, formed from the N-acetyl chloramide, by reactions analogous to those observed with alkoxyl radicals. The detection of increasing yields of low-molecular-weight radical adducts from hyaluronic acid and chondroitin sulphate A with increasing HOCl/ClO− concentrations suggests that formation of the initial nitrogen-centered species on the N-acetylglucosamine rings, and the carbon-centered radicals derived from them, brings about polymer fragmentation. 相似文献
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Towards the physiological function of uric acid 总被引:48,自引:0,他引:48
Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiology value. However, this ubiquitous compound has proven to be selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidase cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urates is the microvascular endothelium, and there is generally a net release of urate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant. 相似文献
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Activated phagocytic cells generate hypochlorite (HOCl) via release of hydrogen peroxide and the enzyme myeloperoxidase. HOCl plays an important role in bacterial cell killing, but excessive or misplaced production of HOCl is also known to cause tissue damage. Studies have shown that low-molecular-weight thiols such as reduced glutathione (GSH), and sulfur-containing amino acids in proteins, are major targets for HOCl. Radicals have not generally been implicated as intermediates in thiol oxidation by HOCl, though there is considerable literature evidence for the involvement of radicals in the metal ion-, thermal- or UV light-catalysed decomposition of sulfenyl or sulfonyl chlorides which are postulated intermediates in thiol oxidation. In this study we show that thiyl radicals are generated on reaction of a number of low-molecular-weight thiols with HOCl. With sub-stoichiometric amounts of HOCl, relative to the thiol, thiyl radicals are the major species detected by EPR spin trapping. When the HOCl is present in excess over the thiol, additional radicals are detected with compounds which contain amine functions; these additional radicals are assigned to nitrogen-centered species. Evidence is presented for the involvement of sulfenyl chlorides (RSCl) in the formation of these radicals, and studies with an authentic sulfenyl chloride have demonstrated that this compound readily decomposes in thermal-, metal-ion- or light-catalysed reactions to give thiyl radicals. The formation of thiyl radicals on oxidation of thiols with HOCl appears to compete with non-radical reactions. The circumstances under which radical formation may be important are discussed. 相似文献