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When life first evolved on Earth, there was little oxygen in the atmosphere. Evolution of antioxidant defences must have been closely associated with the evolution of photosynthesis and of O2-dependent electron transport mechanisms. Studies with mice lacking antioxidant defences confirm the important roles of MnSOD and transferrin in maintaining health, but show that glutathione peroxidase (GPX) and CuZnSOD are not essential for everyday life (at least in mice). Superoxide can be cytotoxic by several mechanisms: one is the formation of hydroxyl radicals. There is good evidence that OH· formation occurs in vivo. Other important antioxidants may include thioredoxin, and selenoproteins other than GPX. Nitric oxide may be an important antioxidant in the vascular system. Diet-derived antioxidants are important in maintaining human health, but recent studies employing "biomarkers" of oxidative DNA damage are questioning the "antioxidant" roles of β-carotene and ascorbate. An important area of future research will be elucidation of the reasons why levels of steady-state oxidative damage to DNA and lipids vary so much between individuals, and their predictive value for the later development of human disease.
There has been a recent surge of interest in the unique low molecular weight dietary thiol/thione, ergothioneine. This compound can accumulate at high levels in the body from diet and may play important physiological roles in human health and development, and possibly in prevention and treatment of disease. Blood levels of ergothioneine decline with age and onset of various diseases. Here we highlight recent advances in our knowledge of ergothioneine.
The neutrophil enzyme myeloperoxidase generates hypochlorous acid (HOCl) at sites of inflammation. Glutathione peroxidase is very quickly inactivated by low concentration of HOCl. Inactivation of catalase is also rapid, but requires higher HOCl concentrations and the haem appears to be degraded. Inactivation of bovine CuZn superoxide dismutase is slower. Hence superoxide dismutase should not be easily inactivated by HOCl at sites of inflammation, which may contribute to its effectiveness as an anti-inflammatory agent and in minimizing reperfusion injury.
Conference Article| August 01 1991 Iron speciation in hypotransferrinaemic mouse serum R. J. SIMPSON; R. J. SIMPSON 1Dept. of Clinical Biochemistry, King's College School of Medicine and Dentistry, Bessemer Rd., London SE5 Search for other works by this author on: This Site PubMed Google Scholar K. B. RAJA; K. B. RAJA 1Dept. of Clinical Biochemistry, King's College School of Medicine and Dentistry, Bessemer Rd., London SE5 Search for other works by this author on: This Site PubMed Google Scholar B. HALLIWELL; B. HALLIWELL *Dept of Biochemistry, King's College, The Strand, London Search for other works by this author on: This Site PubMed Google Scholar P. J. EVANS; P. J. EVANS *Dept of Biochemistry, King's College, The Strand, London Search for other works by this author on: This Site PubMed Google Scholar O. I. ARUOMA; O. I. ARUOMA *Dept of Biochemistry, King's College, The Strand, London Search for other works by this author on: This Site PubMed Google Scholar A. M. KONIJN; A. M. KONIJN #Dept. Nutrition. The Hebrew University-Hadassah Medical School, Jerusalem, Israel Search for other works by this author on: This Site PubMed Google Scholar T. J. PETERS T. J. PETERS 1Dept. of Clinical Biochemistry, King's College School of Medicine and Dentistry, Bessemer Rd., London SE5 Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1991 Biochemical Society1991 Biochem Soc Trans (1991) 19 (3): 317S. https://doi.org/10.1042/bst019317s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation R. J. SIMPSON, K. B. RAJA, B. HALLIWELL, P. J. EVANS, O. I. ARUOMA, A. M. KONIJN, T. J. PETERS; Iron speciation in hypotransferrinaemic mouse serum. Biochem Soc Trans 1 August 1991; 19 (3): 317S. doi: https://doi.org/10.1042/bst019317s Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
A highly sensitive HPLC method for the separation of hydroxylation products derived from the attack of hydroxyl radical upon phenol is described. Catechol and hydroquinone are the major hydroxylation products formed, with little resorcinol. The effect of EDTA upon hydroxyl radical generation from an iron (H)-H2O2 system is shown to depend upon the order of addition of chelator and metal ion to the reaction mixture, the ratio [iron salt]/[chelator] and the presence or absence of a phosphate buffer. Reasons for these different effects are discussed.
The water-soluble thione/thiol ergothioneine (ET) was first isolated in 1909 by Charles Tanret [1], from the ergot fungus Claviceps purpurea. This fungus is notorious for the toxicity of some of its metabolites to humans, causing ergotism [2], which has even been linked to the Salem witch trials [3]. However, ergotism has nothing to do with ET, which is instead very safe for human consumption and is synthesized by a range of other fungi and some bacteria (reviewed in [4-9]). Its biosynthetic pathways are reviewed in detail in [6]. Indeed, as far as we know, humans and other animals obtain all their ET from the diet [4, 5, 7-10], whereas plants seem to obtain it from fungi and other soil microorganisms [9]. An enormous amount of work was done on ET in the 1950s, as summarized in the excellent review by Melville [7]. Interest then waned but has picked up rapidly in recent years (Fig. 1). We, therefore, thought that it was about time for a collection of articles and reviews highlighting the recent developments in the ET field. We, thus, approached both FEBS Letters, which was very supportive, and a range of experts working on ET, who were almost uniformly enthusiastic and happy to contribute. The FEBS Letters Special Issue 'Ergothioneine, where are we now?' is the result of these activities and contains 11 articles by leading experts. One catalyst for this upsurge of interest was the discovery in 2005 of a transporter for ET (OCTN1, often now called the ergothioneine transporter, ETT), which accounts for the fact that animals (including humans) take up and avidly retain ET from the diet [11]. The specificity of ETT for ET has often been challenged but has been reconfirmed in several studies [11-13], as reviewed in depth by Grundemann et al. in this special issue [14]. The presence of a specific transporter together with the avid retention of ET in the body implies that this compound is important to us, and indeed in 2018 Bruce Ames proposed that ET be classified as a 'longevity vitamin' [15]. No specific deficiency disease has yet been identified for ET, which makes it hard to formally classify it as a vitamin. Perhaps, however, deficiency diseases are staring us in the face: low blood or plasma levels of ET are correlated with increased risk of frailty [16-18], cardiovascular disease [19], mild cognitive impairment [18, 20-22], dementia [22, 23] and Parkinson's disease [24]. Indeed, ET has many neuroprotective properties [4, 5, 18, 26, 27], as reviewed in detail in this special issue [18, 25, 26]. Consistent with a key protective role of ET against the development of age-related diseases, higher dietary consumption of mushrooms, a rich source of ET [9], is associated with lower disease risk [28-31]. However, we must be cautious; to quote an old phrase 'correlation does not imply causation'. Low ET levels may predispose to disease, but disease could also lead to low ET levels. Possible reasons could include alterations in diet due to illness so that less ET is consumed, and/or decreases in ETT activity in the gut (leading to less ET uptake) or kidney (impairing ET reabsorption) with age and disease. Changes in gut microbiota might also influence uptake and accumulation in the body, as discussed in this special issue [10]. Indeed, changes in gut microbiota have been associated with a growing number of disorders; however, further work is still needed to explore the association between gut microbiota and ET uptake. Another possibility is that ET is being consumed as it scavenges oxygen radicals and other reactive oxygen species [4, 5, 32], the production of which is known to increase in these diseases and during ageing in general (reviewed in [33-36]). Much early work focused on the antioxidant properties of ET (reviewed in [4, 5, 7]), but this may be too narrow a view of its protective properties [37]. ET as an antioxidant may only come into play at sites of tissue injury, when it seems to be deliberately accumulated by the tissue to help protect it, by raising the amount of ETT and hence the level of ET [24, 38]. In addition, ET has a wide range of other cytoprotective properties that could be relevant in vivo (reviewed in [4, 5, 39-41]. It may even help protect against colon cancer [42]. So, what will happen in the next few years? Hopefully, the value of ET in preventing and treating human disease will become clearer. Animal studies look promising ([27] and much work in progress). However, only the gold standard of placebo-controlled double-blinded clinical studies can definitively establish the value (if any) of ET in preventing or treating human disease. Several such trials are being planned or in progress; we await the results with interest, and a streak of optimism. Other applications of ET such as its use as a food preservative [43] and in cosmetics [44] are also being explored. In addition, there are many facets of ET biology yet to be explained, such as its presence at exceptionally high levels in the seminal fluid of stallions and boars, much less in this fluid from other species [45], and its possible involvement in human development, as seen from the ability of mothers to pass ET to the baby (discussed in [46]). Indeed, these are exciting times for the ET field, including new methods to identify [49] and produce [50] it. We hope that this special issue of FEBS Letters will raise awareness of this unique compound. Barry Halliwell is a Distinguished Professor and Senior Advisor (Academic Appointments and Research Excellence) to the Provost at the National University of Singapore (NUS). He is also Chairman of the Biomedical Research Advisory Council of Singapore's Agency for Science, Technology and Research (A*STAR). His research focuses on the role of reactive oxygen species and antioxidants in human health and disease, with special attention paid to ergothioneine [4,5], which his group helped to characterize many years ago [47, 48]. Irwin Cheah is a Senior Research Fellow at the Department of Biochemistry, Yong Loo Lin School of Medicine and Life Science Institute, NUS. With a long-standing interest in the role of oxidative damage and inflammation in disease and natural therapeutics to counteract these pathological mechanisms, he was naturally drawn to ergothioneine. In recent years, the primary focus of his research has been elucidating the role of ergothioneine in health and disease and establishing its potential therapeutic value in a range of disorders.
Copper (Cu2+) ions at physiological concentrations can promote the formation of hydroxyl radical (OH.) or a species of equivalent reactivity. The reaction requires H2O2 and a reducing agent. Reduction of Cu2+ can be achieved by superoxide ion generated by a mixture of hypoxanthine and xanthine oxidase or added directly as its potassium salt. Reduction of Cu2+ can also be achieved by ascorbic acid. Hence both O2 .−-dependent and ascorbate-dependent formation of OH. from H2O2 in the presence of Cu2+ can be observed. Only the former reaction is significantly inhibited by superoxide dismutase. The binding of Cu2+ to histidine or albumin at physiological concentrations decreases the formation of OH. radicals in free solution in the presence of either ascorbate or an O2 .−-generating system. It is suggested that OH. is still formed but reacts immediately with the binding molecule.
