Editorial: Sulfation Pathways—There and Back Again

Sulfation Pathways are understood as the oxidative branch of sulfur metabolism (Günal et al., 2019).Core to sulfation pathways is sulfate activation, the transfer of sulfate to biological acceptor molecules and its dynamic cleavage in a spatially and temporally specific manner.The biochemical problem of sulfate activation is evident even in geological specimens-gypsum may be observed in orthopedic casts, an example of the highly inert sulfate ion (Figure 1).A significant amount of energy is needed to turn biological sulfate into PAPS (3′-phosphoadenosine-5′-phospho-sulfate), the active sulfate form.The many and diverse sulfation acceptor molecules in biology dictate the molecular functions of ubiquitous sulfation pathways.Recent publications have highlighted doubly sulfated steroids (Lightning et al., 2021) as well as sulfo-conjugated vitamin D species (Jenkinson et al., 2022).This Research Topic focused on Advances in Sulfation Pathways Research features nine research articles and three reviews, authored by 63 individual scientists, significantly advancing the field of Sulfation Pathways, highlighted within the following paragraphs:Research into sulfation pathways always relied on state-of-the-art analytical methods.Hence, we are pleased to present novel mass-spectrometry-based ways of profiling sulfated metabolites in urine by Fitzgerald et al.Developing mass spectrometry methods is impossible however without having the respective pure compounds readily at hand.In this regard, Alshehri et al. report a novel sulfation strategy to prepare steroid sulfates and isotopically labeled variations thereof, certainly an innovation with great importance for the field.Whenever coming from a genomic viewpoint, it may be necessary to characterize a sulfation enzyme with regards to its activity.With this in mind, Sun et al. have prepared a manuscript on optimized sulfotransferase assays.Sulfation impacts greatly on steroidogenesis-sulfated steroids may represent transport forms and/or modulate downstream processing (Foster and Mueller, 2018).Two studies by Pavlič et al. and De Almeida Da Costa et al. independently provide experimental evidence that endometrial tissues can generate estrogens from circulating steroid sulfates.Sulfation of steroids predominantly occurs within the cytosol and sulfated steroids then need dedicated transporters to enter circulation and for the uptake into target tissues.Karakus et al. provide an in-depth study about the steroid sulfate uptake transporter SOAT (SLC10A6) in adipose tissue that illustrates this well.When studying sulfated steroids, not only are circulating steroids important, but also sulfated neuro-steroids.This Research Topic features two review articles about steroid sulfation in neurodegenerative diseases by Vitku et al. and during neurodevelopment by Clarke et al.Fascinating topics that will enable exciting discoveries in future, with great potential for the development of novel therapeutics.

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