2381-08-0Relevant articles and documents
Antioxidant chemistry: Reactivity and oxidation of DL-cysteine by some common oxidants
Darkwa, James,Mundoma, Claudius,Simoyi, Reuben H.
, p. 1971 - 1978 (1998)
The reactivity of DL-cysteine, a physiologically important aminothiol, was studied by reacting it with several well known oxidants. No activity was observed on the amino and carboxyl groups. The only reactivity of physiological significance was at the sulfur centre. Reactions of cysteine with hydrogen peroxide show that the thiol group is capable of mopping up free radicals by forming thyl radicals, as expected in its role as an antioxidant. A four-electron oxidation of cysteine gave reasonably stable cysteine sulfinic acid. Oxidants in the form of peracids do oxidize cysteine only as far as the sulfinic acid. Stronger oxidizing agents can oxidize cysteine as far as the cysteine sulfonic acid. No further oxidation can be detected as the C-S bond is not cleaved. The inertness of the amino group in cysteine makes it incapable of reversibly mopping up the dangerous oxyhalogens HOCl and HOBr which are produced by myeloperoxidase-catalysed oxidation of halides by hydrogen peroxide, as is the case with taurine. A detailed mechanism, together with a computer simulation study of the oxidation of cysteine by acidified bromate, is proposed.
The cysteine dioxygenase homologue from Pseudomonas aeruginosa is a 3-mercaptopropionate dioxygenase
Tchesnokov, Egor P.,Fellner, Matthias,Siakkou, Eleni,Kleffmann, Torsten,Martin, Lois W.,Aloi, Sekotilani,Lamont, Iain L.,Wilbanks, Sigurd M.,Jameson, Guy N.L.
, p. 24424 - 24437 (2015/10/19)
Thiol dioxygenation is the initial oxidation step that commits a thiol to important catabolic or biosynthetic pathways. The reaction is catalyzed by a family of specific non-heme mononuclear iron proteins each of which is reported to react efficiently with only one substrate. This family of enzymes includes cysteine dioxygenase, cysteamine dioxygenase, mercaptosuccinate dioxygenase, and 3-mercaptopropionate dioxygenase. Using sequence alignment to infer cysteine dioxygenase activity, a cysteine dioxygenase homologue from Pseudomonas aeruginosa (p3MDO) has been identified. Mass spectrometry of P. aeruginosa under standard growth conditions showed that p3MDO is expressed in low levels, suggesting that this metabolic pathway is available to the organism. Purified recombinant p3MDO is able to oxidize both cysteine and 3-mercaptopropionic acid in vitro, with a marked preference for 3-mercaptopropionic acid. We therefore describe this enzyme as a 3-mercaptopropionate dioxygenase. M?ssbauer spectroscopy suggests that substrate binding to the ferrous iron isthrough the thiol but indicates that each substrate could adopt different coordination geometries. Crystallographic comparison with mammalian cysteine dioxygenase shows that the overall active site geometry is conserved but suggests that the different substrate specificity can be related to replacement of an arginine by a glutamine in the active site.
Kinetics and mechanism for the reaction of cysteine with hydrogen peroxide in amorphous polyvinylpyrrolidone lyophiles
Luo, Dayong,Anderson, Bradley D.
, p. 2239 - 2253 (2007/10/03)
Purpose. Peroxide impurities play a critical role in drug oxidation. In metal-free aqueous solutions, hydrogen peroxide (H2O2) induced thiol oxidation involves a bimolecular nucleophilic reaction to form a reactive sulfenic acid intermediate (RSOH), which reacts with a second thiol to form a disulfide (RSSR). This study examines the reaction of cysteine (CSH) and H2O2 in amorphous polyvinylpyrrolidone (PVP) lyophiles to explore the possible relevance of the solution mechanism to reactivity in an amorphous glass. Materials and Methods. Amorphous PVP lyophiles containing CSH and H2O2 at varying initial 'pH' and reactant concentrations were prepared by methods designed to minimize reaction during lyophilization. Kinetic studies were conducted anaerobically at 25°C and reactants and products were monitored by HPLC. Products were characterized and the kinetic data were fit to models adapted from the solution mechanism. Results. Key differences in the reactions in aqueous solution and amorphous PVP are: (1) while only cystine (CSSC) forms in solution, three degradants-cysteine sulfinic acid (CSO2H), cysteine sulfonic acid (CSO3H) and cystine (CSSC)-form in amorphous PVP; (2) simple bimolecular kinetics govern the solution reaction while initial rates in amorphous PVP suggested more complex kinetics (i.e., non-unity values for reaction order); and (3) heterogeneous (i.e., biphasic) reaction dynamics are evident in amorphous PVP. The differences in product formation and apparent reaction orders in the solid-state could be rationalized by partitioning of the same reactive intermediate to multiple products in the solid-state due to the restricted mobility of CSH. Beyond the initial rate region, the kinetics in amorphous PVP could be described by the Kohlrausch-Williams-Watts (KWW) stretched-exponential equation or by assuming two populations of reactant molecules having different reactivities. Conclusions. When reactive intermediates are involved, differences in degradant profiles and other characteristics (e.g., rate constants, apparent reaction order) in the amorphous-state may simply reflect altered rates for individual reaction steps due to glass-induced changes in relative reactant mobilities rather than a change in overall mechanism.
