H2S/Thiols, NO•, and NO–/HNO: Interactions with Iron Porphyrins

Bieza, Silvina Andrea; Mazzeo, Agostina; Pellegrino, Juan; Doctorovich, Fabio

doi:10.1021/acsomega.1c06427

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…In this context, the current findings place cyanide – together with NO, CO and H 2 S – in the group of mammalian regulatory gasotransmitter species (Extended Data Table 11). These gases play various regulatory roles, which are sometimes distinct, sometimes overlapping, and sometimes cooperative 1,6,52–56 . Further studies remain to be conducted to further characterize the role of endogenous cyanide in mammalian cells and tissues.…”

Section: Discussionmentioning

confidence: 99%

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Zuhra,

Petrosino,

Janickova

et al. 2024

Preprint

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Small, gaseous molecules, known as gasotransmitters (NO, CO, H2S), are produced endogenously in mammalian cells and serve important biological roles. Hydrogen cyanide, traditionally considered a cytotoxic molecule in mammals, serves as an endogenous mediator in several plants and bacterial species. Here we show that low concentrations of cyanide are generated endogenously in mouse liver and human hepatocytes. Cyanide production is stimulated by glycine, occurs at the low pH of lysosomes and requires peroxidase activity. Cyanide, in turn, is detectable in several cellular compartments. Cyanide is also detectable basally in the blood of mice; its levels increase after treatment of the animals with glycine. Rhodanese activity regulates endogenous cyanide levels. Cyanide, when generated endogenously at an optimal level, exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism and cell proliferation. Dysregulation of endogenous cyanide, either below or above optimal levels, impairs cellular bioenergetics. The regulatory effects of cyanide are in part mediated by posttranslational modification of cysteine residues via protein cyanylation; cyanylated protein residues can be detected basally, and increase after treatment with glycine. Controlled low-dose cyanide supplementation exhibits cytoprotective effects, as demonstrated in hypoxia and reoxygenation modelsin vitroandin vivo. However, pathologically elevated cyanide production, as demonstrated in nonketotic hyperglycinemia – an autosomal recessive disease of glycine metabolism – is deleterious to the cells.

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Section: Discussionmentioning

confidence: 99%

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Zuhra,

Petrosino,

Janickova

et al. 2024

Preprint

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“…They also provided evidence of the catalytic hydrogenation activity of Fe-porphyrin on the levels of proteins and cells, such as the catalytic activity of Hb for the hydrogenation of hydroxyl radicals and the reduction of CO 2 by H 2 into CO through Fe-porphyrin-catalytic hydrogenation. Heme proteins can also interact with other gaseous molecules, such as CO, NO, O 2 , and H 2 S, which play vital roles in many biological processes [105,106]. Thus, it is likely that H 2 competes with them to interact with heme proteins, which ultimately affects the physiological functions of these gaseous molecules.…”

Section: Other Possible Mechanisms and Potential Molecular Targets Of Hmentioning

confidence: 99%

Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside

Xie

Song

et al. 2023

Pharmaceuticals

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Oxidative stress and chronic inflammation have been implicated in the pathophysiology of metabolic diseases, including diabetes mellitus (DM), metabolic syndrome (MS), fatty liver (FL), atherosclerosis (AS), and obesity. Molecular hydrogen (H2) has long been considered a physiologically inert gas. In the last two decades, accumulating evidence from pre-clinical and clinical studies has indicated that H2 may act as an antioxidant to exert therapeutic and preventive effects on various disorders, including metabolic diseases. However, the mechanisms underlying the action of H2 remain unclear. The purpose of this review was to (1) provide an overview of the current research on the potential effects of H2 on metabolic diseases; (2) discuss the possible mechanisms underlying these effects, including the canonical anti-oxidative, anti-inflammatory, and anti-apoptotic effects, as well as suppression of ER stress, activation of autophagy, improvement of mitochondrial function, regulation of gut microbiota, and other possible mechanisms. The potential target molecules of H2 will also be discussed. With more high-quality clinical trials and in-depth mechanism research, it is believed that H2 will eventually be applied to clinical practice in the future, to benefit more patients with metabolic disease.

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“…In parallel with advancements in the molecular recognition of small anionic guests has been the expansion and recognition of small molecule signaling molecules in the adjacent fields of chemical biology and pharmacology. Many of these species stem from endogenously produced signaling molecules like H 2 S and related species, which have garnered significant attention over the last two decades due to their complex and entwined roles in ubiquitous biological processes. , H 2 S is established to reduce oxidative stress, promote vasodilation, and exert cardioprotection, in addition to other biological functions. , What makes small molecules good cellular signaling agents also makes them difficult to study, specifically their propensity to react rapidly with other biomolecules or through different redox pathways. − Moreover, this high reactivity also suggests that specific molecular environments may stabilize or recognize these highly reactive species through specific types of interactions or recognition environments. Although generally written as its diprotic neutral form, H 2 S exists primarily as hydrosulfide (HS – ) at physiological pH.…”

Section: Introductionmentioning

confidence: 99%

Reversible Hydrosulfide (HS^–) Binding Using Exclusively C–H Hydrogen-Bonding Interactions in Imidazolium Hosts

Davis,

Zakharov,

Pluth

2024

Inorg. Chem.

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H2S is a physiologically important signaling molecule with complex roles in biology and exists primarily as HS– at physiological pH. Despite this anionic character, few investigations have focused on the molecular recognition and reversible binding of this important biological anion. Using a series of imidazole and imidazolium host molecules, we investigate the role of preorganization and charge on HS– binding. Using a macrocyclic bis-imidazolium receptor, we demonstrate the unexpected 2:1 host−guest binding of HS–, which was characterized both in solution and by X-ray crystallography. To the best of our knowledge, this is the first example of this binding stoichiometry for HS– binding. Moreover, the short C–H···S distances of 2.53, 2.54, 2.76, and 2.79 Å are well within the sum of the van der Waals radii of the interacting atoms, which is consistent with strong C–H···S interactions.

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H₂S/Thiols, NO^•, and NO^–/HNO: Interactions with Iron Porphyrins

Cited by 5 publications

References 34 publications

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside

Reversible Hydrosulfide (HS^–) Binding Using Exclusively C–H Hydrogen-Bonding Interactions in Imidazolium Hosts

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H2S/Thiols, NO•, and NO–/HNO: Interactions with Iron Porphyrins

Cited by 5 publications

References 34 publications

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Endogenously produced hydrogen cyanide serves as a novel mammalian gasotransmitter

Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside

Reversible Hydrosulfide (HS–) Binding Using Exclusively C–H Hydrogen-Bonding Interactions in Imidazolium Hosts

Contact Info

Product

Resources

About

H₂S/Thiols, NO^•, and NO^–/HNO: Interactions with Iron Porphyrins

Reversible Hydrosulfide (HS^–) Binding Using Exclusively C–H Hydrogen-Bonding Interactions in Imidazolium Hosts