Abstract
The biology of the macro-element sulfur (S) is attracting an ever growing attention concerning cell physiology and human health. Sulfur metabolism works at the interplay between genetics and epigenetic as well as in the maintain of cell redox homeostasis. Indeed, unbalanced levels of S compounds in the body are actually under investigation as vulnerability factors and/or indicators of impaired cell oxidation state in a variety of human diseases. The purpose of this article is to overview some main S metabolic pathways in humans and their relevance in cell physiology and pathology. Since S is an essential nutrient for life, we first present its distribution and significance in the biosphere, focusing then on S metabolic fluxes which encompass S-containing amino acids (S-AAs), as well as sulfoconjugation, the synthesis and release of H2S together the formation of iron-sulfur cluster proteins. Despite the vastness of the topic, we would like to emphasize herein that the study of S networks in human pathology, especially in complex, multi-factorial disorders, deserves greater impulsion and deepening.
Highlights
Among chemical element essential for life, the mineral sulfur (S) presents an unexpected complexity of bioactive derivatives that makes difficult to fully define its tissue distribution, metabolic fates and requirements for humans
A major input to deepen S biology and its impact on human health comes from results obtained in these last decades by the scientific community showing the relevance of S-containing biomolecules, as S-amino acids (S-AAs), reduced γ-L-Glutamyl-L-cysteinylglycine or 3’-phosphoadenosine 5’-phosphosulfate (PAPS) in a variety of homeostatic processes in the body
If S biology is intricate, this area of investigation proves to be, at the same time, really fascinating: the widespread presence and diversity of organosulfur bioactive molecules in living organisms can be explained by the fact that this macro-element was one of the predominant atoms on Earth before life and the origin of life has been even attributed to S chemistry
Summary
Among chemical element essential for life, the mineral sulfur (S) presents an unexpected complexity of bioactive derivatives that makes difficult to fully define its tissue distribution, metabolic fates and requirements for humans. Sulfur biomolecules exert important functions in all living organisms and their transformations are involved in metals’ transport, free radicals scavenging, tissue integrity protection, enzyme functionality, DNA methylation and repair, regulation of gene expression, protein synthesis, remodeling of extracellular matrix components, lipid metabolism and detoxification of xenobiotics/ signaling molecules in plants and animals [1,2]. The study of S biochemistry provides further evidence to the hypothesis that cell evolution has been favored by mechanisms of interaction, exchange and transformation involving prokaryote and eukaryote genomes [5]. It follows that S species and S-containing biomolecules occupy a foremost position in metabolism, even from the evolutionary standpoint, an issue which deserves special attention for ecosystems and human health. Because of the complexity of S biochemistry, we have divided the review on S compounds and human health in two parts: the present, a first and more general section, which overviews some main S metabolism substrates, mentioning their involvement in human pathology, especially in complex, multi-factorial disorders; a second one which will deal with data obtained from the literature in clinical research showing S metabolism variation in specific complex diseases as autism spectrum disorders (ASD), schizophrenia and fibromyalgia, by outlining their significance and future perspectives
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