Oxidation effects on tetrahydropterin metabolism

The susceptibility of tetrahydropterins to oxidation was investigated in vitro and related to in vivo metabolism. At physiological pH, tetrahydrobiopterin (BH4) was oxidized, with considerable loss of the biopterin skeleton, by molecular oxygen. The hydroxyl radical (.OH) was found to increase this oxidation and degradation, whilst physiological concentrations of glutathione (GSH) retarded both the dioxygen and .OH mediated oxidation. Nitrite, at acid pH, oxidized BH4 to biopterin and tetrahydrofolates to products devoid of folate structure. Loss of dietary folates, from the stomach, due to nitrite mediated catabolism is suggested. The in vivo response of BH4 metabolism to oxidising conditions was examined in the rat brain and liver. Acute starvation depressed brain biopterins and transiently BH4 biosynthetic and salvage (dihydropteridine reductase, DHPR) pathways. Loss of biopterins, in starvation, is suggested to arise primarily from catabolism, due to oxygen radical formation and GSH depletion. L-cysteine administration to starving rats was found to elevate tissue biopterins, whilst depletion of GSH in feeding rats, by L-buthionine sulfoximine, decreased biopterins. An in vivo role for GSH to protect tetrahydropterins from oxidation is suggested. The in vivo effect of phenelzine dosing was investigated. Administration lowered brain biopterins, in the presence of dietary tyrosine. This loss is considered to arise from p-tyramine generation and subsequent DHPR inhibition. Observed elevations in plasma biopterins were in line with this mechanism. In conditions other than gross inhibition of DHPR or BH4 biosynthesis, plasma total biopterins were seen to be poor indicators of tissue BH4 metabolism. Evidence is presented indicating that the pterin formed in tissue samples by acid iodine oxidation originates from the tetrahydrofolate pool and 7,8-dihydropterin derived from BH4 oxidation. The observed reduction in this pterin by prior in vivo nitrous oxide exposure and elevation by starvation and phenelzine administration is discussed in this light. The biochemical importance of the changes in tetrahydropterin metabolism observed in this thesis are discussed with extrapolation to the situation in man, where appropriate. An additional role for BH4 as a tissue antioxidant and reductant is also considered.

Effect of extrusion and photo-oxidation on polyethylene/clay nanocomposites

Polyethylene (a 1:1 blend of m-LLDPE and z-LLDPE) double layer silicate clay nanocomposites were prepared by melt extrusion using a twin screw extruder. Maleic anhydride grafted polyethylene (PEgMA) was used as a compatibiliser to enhance the dispersion of two organically modified monmorilonite clays (OMMT): Closite 15A (CL15) and nanofill SE 3000 (NF), and natural montmorillonite (NaMMT). The clay dispersion and morphology obtained in the extruded nanocomposite samples were fully characterised both after processing and during photo-oxidation by a number of complementary analytical techniques. The effects of the compatibiliser, the organoclay modifier (quartenary alkyl ammonium surfactant) and the clays on the behaviour of the nanocomposites during processing and under accelerated weathering conditions were investigated. X-ray diffraction, transmission electron microscopy (TEM), scanning electron microscopy (SEM), rheometry and attenuated reflectance spectroscopy (ATR-FTIR) showed that the nanocomposite structure obtained is dependent on the type of clay used, the presence or absence of a compatibiliser and the environment the samples are exposed to. The results revealed that during processing PE/clay nanocomposites are formed in the presence of the compatibiliser PEgMA giving a hybrid exfoliated and intercalated structures, while microcomposites were obtained in the absence of PEgMA; the unmodified NaMMT-containing samples showed encapsulated clay structures with limited extent of dispersion in the polymer matrix. The effect of processing on the thermal stability of the OMMT-containing polymer samples was determined by measuring the additional amount of vinyl-type unsaturation formed due to a Hoffman elimination reaction that takes place in the alkyl ammonium surfactant of the modified clay at elevated temperatures. The results indicate that OMMT is responsible for the higher levels of unsaturation found in OMMT-PE samples when compared to both the polymer control and the NaMMT-PE samples and confirms the instability of the alkyl ammonium surfactant during melt processing and its deleterious effects on the durability aspects of nanocomposite products. The photostability of the PE/clay nanocomposites under accelerated weathering conditions was monitored by following changes in their infrared signatures and mechanical properties. The rate of photo-oxidation of the compatibilised PE/PEgMA/OMMT nanocomposites was much higher than that of the PE/OMMT (in absence of PEgMA) counterparts, the polymer controls and the PE–NaMMT sample. Several factors have been observed that can explain the difference in the photo-oxidative stability of the PE/clay nanocomposites including the adverse role played by the thermal decomposition products of the alkyl ammonium surfactant, the photo-instability of PEgMA, unfavourable interactions between PEgMA and products formed in the polymer as a consequence of the degradation of the surfactant on the clay, as well as a contribution from a much higher extent of exfoliated structures, determined by TEM, formed with increasing UV-exposure times.

Redox signalling and detection of protein oxidation by mass spectrometry

It is now recognised that redox control of proteins plays an important role in many signalling pathways both in health and disease. Proteins can undergo a wide variety of oxidative post-translational modifications (oxPTM); while the reversible modifications are thought to be most important in physiological processes, non-reversible oxPTM may contribute to pathological situations and disease. The oxidant is also important in determining the type of oxPTM (chlorination, nitration, etc.), and the susceptibilities of residues vary depending on their structural location. The best characterized oxPTMs involved in signalling modulation are partial oxidations of cysteine to the disulfide, glutathionylated or sulfenic acid forms, but there is increasing evidence that specific oxidations of methionine and tyrosine may have some biological roles. Well understood examples of oxidative regulation include protein tyrosine phosphatases, e.g. PTP1B/C, and members of the MAPK pathways such as MEKK1 and ASK1. Transcription factors such as NFkB and Nrf-2 are also regulated by redox-active cysteines. Improved methods for analysing specific oxPTMs in biological samples are critical for understanding the physiological and pathological roles of these changes, and tandem or MS3 mass spectrometry techniques interfaced with nano-LC separation are being now used. MS3 fragmentation markers for a variety of oxidized residues including tyrosine, tryptophan and proline have been identified, and a precursor ion scanning method that allows the selective identification of these oxPTMs in complex samples has been developed. Such advances in technology offer potential for biomarker development, disease diagnosis and understanding pathology.

Chemistry of phospholipid oxidation

The oxidation of lipids has long been a topic of interest in biological and food sciences, and the fundamental principles of non-enzymatic free radical attack on phospholipids are well established, although questions about detail of the mechanisms remain. The number of end products that are formed following the initiation of phospholipid peroxidation is large, and is continually growing as new structures of oxidized phospholipids are elucidated. Common products are phospholipids with esterified isoprostane-like structures and chain-shortened products containing hydroxy, carbonyl or carboxylic acid groups; the carbonyl-containing compounds are reactive and readily form adducts with proteins and other biomolecules. Phospholipids can also be attacked by reactive nitrogen and chlorine species, further expanding the range of products to nitrated and chlorinated phospholipids. Key to understanding the mechanisms of oxidation is the development of advanced and sensitive technologies that enable structural elucidation. Tandem mass spectrometry has proved invaluable in this respect and is generally the method of choice for structural work. A number of studies have investigated whether individual oxidized phospholipid products occur in vivo, and mass spectrometry techniques have been instrumental in detecting a variety of oxidation products in biological samples such as atherosclerotic plaque material, brain tissue, intestinal tissue and plasma, although relatively few have achieved an absolute quantitative analysis. The levels of oxidized phospholipids in vivo is a critical question, as there is now substantial evidence that many of these compounds are bioactive and could contribute to pathology. The challenges for the future will be to adopt lipidomic approaches to map the profile of oxidized phospholipid formation in different biological conditions, and relate this to their effects in vivo. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins.

Reaction-driven surface restructuring and selectivity control in allylic alcohol catalytic aerobic oxidation over Pd

Synchronous, time-resolved DRIFTS/MS/XAS cycling studies of the vapor-phase selective aerobic oxidation of crotyl alcohol over nanoparticulate Pd have revealed surface oxide as the desired catalytically active phase, with dynamic, reaction-induced Pd redox processes controlling selective versus combustion pathways.

Stabilising cysteinyl thiol oxidation and nitrosation for proteomic analysis

Oxidation and S-nitrosylation of cysteinyl thiols (Cys-SH) to sulfenic (Cys-SOH), sulfinic (Cys-SO2H), sulfonic acids (Cys-SO3H), disulphides and S-nitrosothiols are suggested as important post-translational modifications that can activate or deactivate the function of many proteins. Non-enzymatic post-translational modifications to cysteinyl thiols have been implicated in a wide variety of physiological and pathophysiological states but have been difficult to monitor in a physiological setting because of a lack of experimental tools. The purpose of this review is to bring together the approaches that have been developed for stably trapping cysteine either in its reduced or oxidised forms for enrichment and or subsequent mass spectrometric analysis. These tools are providing insight into potential targets for post-translational modifications to cysteine modification in vivo. This article is part of a Special Issue entitled: Special Issue: Posttranslational Protein modifications in biology and Medicine. © 2013.

Control of spatiotemporal chaos in catalytic CO oxidation by laser-induced pacemakers

Control of spatiotemporal chaos is achieved in the catalytic oxidation of CO on Pt(110) by localized modification of the kinetic properties of the surface chemical reaction. In the experiment, a small temperature heterogeneity is created on the surface by a focused laser beam. This heterogeneity constitutes a pacemaker and starts to emit target waves. These waves slowly entrain the medium and suppress the spatiotemporal chaos that is present in the absence of control. We compare this experimental result with a numerical study of the Krischer-Eiswirth-Ertl model for CO oxidation on Pt(110). We confirm the experimental findings and identify regimes where complete and partial controls are possible.

Suppression of spatiotemporal chaos in the oscillatory CO oxidation on Pt(110) by focused laser light

Chemical turbulence in the oscillatory catalytic CO oxidation on Pt(110) is suppressed by means of focused laser light. The laser locally heats the platinum surface which leads to a local increase of the oscillation frequency, and to the formation of a pacemaker which emits target waves. These waves slowly entrain the medium and suppress the spatiotemporal chaos present in the absence of laser light. Our experimental results are confirmed by a detailed numerical analysis of one- and two-dimensional media using the Krischer-Eiswirth-Ertl model for CO oxidation on Pt110. Different control regimes are identified and the dispersion relation of the system is determined using the pacemaker as an externally tunable wave source.

Effect of preparation conditions on the formation of the active phase of carbon fiber catalytic systems for the low-temperature oxidation of carbon monoxide

We studied the effects of the composition of impregnating solution and heat treatment conditions on the activity of catalytic systems for the low-temperature oxidation of CO obtained by the impregnation of Busofit carbon-fiber cloth with aqueous solutions of palladium, copper, and iron salts. The formation of an active phase in the synthesized catalysts at different stages of their preparation was examined with the use of differential thermal and thermogravimetric analyses, X-ray diffraction analysis, X-ray photoelectron spectroscopy, and elemental spectral analysis. The catalytic system prepared by the impregnation of electrochemically treated Busofit with the solutions of PdCl, FeCl, CuBr, and Cu(NO ) and activated under optimum conditions ensured 100% CO conversion under a respiratory regime at both low (0.03%) and high (0.5%) carbon monoxide contents of air. It was found that the activation of a catalytic system at elevated temperatures (170-180°C) leads to the conversion of Pd(II) into Pd(I), which was predominantly localized in a near-surface layer. The promoting action of copper nitrate consists in the formation of a crystalline phase of the rhombic atacamite CuCl(OH). The catalyst surface is finally formed under the conditions of a catalytic reaction, when a joint Pd(I)-Cu(I) active site is formed. © 2014 Pleiades Publishing, Ltd.

Alkaline nitro-benzene oxidation of model compounds and solid fuel derivatives

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