Sulfur as a Signaling Nutrient Through Hydrogen Sulfide

Abstract

Hydrogen sulfide (H2S) has emerged as an important signaling molecule with beneficial effects on various cellular processes affecting, for example, cardiovascular and neurological functions. The physiological importance of H2S is motivating efforts to develop strategies for modulating its levels. However, advancement in the field of H2S-based therapeutics is hampered by fundamental gaps in our knowledge of how H2S is regulated, its mechanism of action, and its molecular targets. This review provides an overview of sulfur metabolism; describes recent progress that has shed light on the mechanism of H2S as a signaling molecule; and examines nutritional regulation of sulfur metabolism, which pertains to health and disease.

Sulfide Oxidation by a Noncanonical Pathway in Red Blood Cells Generates Thiosulfate and Polysulfides

“…As noted previously, the rate constant for oxygenation of the sulfide radical anion at pH 7.0 and 37°C is 7.5 ϫ 10 9 M Ϫ1 s Ϫ1 (31). Hydrolysis of [5] yields the thiosulfate [6], which following oxidation would yield the ferric product complex [7]. Dissociation of thiosulfate from [7] regenerates MetHb.…”

“…This problem is magnified by the sheer abundance of RBCs in circulation, which in the absence of an H 2 S clearance mechanism, would lead to certain death due to the buildup of toxic levels of H 2 S and its facile permeation across lipid bilayers (2,3). As a signaling molecule, H 2 S elicits profound physiological effects ranging from cardioprotection to being an anti-inflammatory mediator and a neuromodulator (4,5). Three enzymes, cystathionine ␤-synthase (CBS), 2 ␥-cystathionase (CSE), and mercaptopyruvate sulfurtransferase (MST) are primarily responsible for cellular H 2 S biogenesis, and their relative contributions vary in a tissue-specific manner (6,7).…”

“…-Fe II radical anion species [3]. Oxygenation of the ferrous hydrodisulfide radical anion [3] would generate the sulfur dioxide radical derivative [4], which could be oxidized to give [5] and O 2 . .…”

Un nouveau lien entre des taux élevés d’homocystéine, les cancers et les maladies neurodégénératives

“…En fonction des demandes métaboliques, l'HCys est soit recyclée en méthionine, en conjonction avec le métabolisme du folate ou par l'action de la bétaine-homocystéine S-méthyltransférase, soit catabolisée en cystéine (Cys), un acide aminé semi-essentiel précurseur du glutathion (GSH) et de la taurine, via la voie dite de transsulfuration [1,4] (➜) (Figure 1). Cette dernière, qui comprend deux enzymes dépendantes de la vitamine B 6 , la cystathionine--synthase (CBS) et la cystathionine--lyase (CSE), est une source importante de Cys chez les mammifères, son inhibition entraînant une diminution d'environ 50 % des taux de GSH dans les tissus.…”

“…d'hydrogène (H 2 S), un médiateur gazeux récemment identifié. Son catabolisme est directement couplé à la respiration cellulaire et il exerce diverses fonctions de signalisation dans les systèmes vasculaires et neuronaux, et dans la régu-lation de la réponse inflammatoire [1,[5][6][7] (Figure 1). …”