Looking Back at the Early Stages of Redox Biology

Abstract

The beginnings of redox biology are recalled with special emphasis on formation, metabolism and function of reactive oxygen and nitrogen species in mammalian systems. The review covers the early history of heme peroxidases and the metabolism of hydrogen peroxide, the discovery of selenium as integral part of glutathione peroxidases, which expanded the scope of the field to other hydroperoxides including lipid hydroperoxides, the discovery of superoxide dismutases and superoxide radicals in biological systems and their role in host defense, tissue damage, metabolic regulation and signaling, the identification of the endothelial-derived relaxing factor as the nitrogen monoxide radical (more commonly named nitric oxide) and its physiological and pathological implications. The article highlights the perception of hydrogen peroxide and other hydroperoxides as signaling molecules, which marks the beginning of the flourishing fields of redox regulation and redox signaling. Final comments describe the development of the redox language. In the 18th and 19th century, it was highly individualized and hard to translate into modern terminology. In the 20th century, the redox language co-developed with the chemical terminology and became clearer. More recently, the introduction and inflationary use of poorly defined terms has unfortunately impaired the understanding of redox events in biological systems.

Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

“…The term ‘ oxidative stress ’ was first coined by Helmut Sies 1 as an imbalance between production of oxidants and antioxidant defences that may result in damage to biological systems. Since then, the field of redox biology has evolved from concepts of oxidative stress in pathology to redox signalling in physiology 2 – 4 .…”

Selenium-Catalyzed Reduction of Hydroperoxides in Chemistry and Biology

“…The thioredoxin reductases indirectly contribute to this important task by providing reduced thioredoxin, the substrate of the majority of the peroxiredoxins. However, since hydroperoxides are not only toxic compounds that have to be eliminated from living systems, but also important signaling molecules [43,44], an over-optimization of hydroperoxide reduction may lead to unexpected disturbances of metabolic regulation. For instance, overexpression of glutathione peroxidase type 1 did not make mice more robust, but obese and insulin-resistant [45].…”

Synthesis and Applications of Organic Selenols

“…The enzymatic activity of mammalian selenoproteins such as glutathione peroxidase (GPx), [18,19] iodothyronine deiodinase, [20] and thioredoxin reductase (TrxR) [21] relies on the properties of a selenocystein residue and, more specifically, on the reactivity of its selenol moiety (or selenolate anion). For example, the two‐step mechanism explaining the very fast reactivity of GPx relies on the acidity and nucleophilicity of the selenol moiety of the Sec residue present in the enzyme active site.…”