The chemical biology of hydrogen sulfide and related hydropersulfides: interactions with biologically relevant metals and metalloproteins

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Abstract

Hydrogen sulfide and related/derived persulfides (RSnH, RSSnR, n > 1) have been the subject of recent research interest because of their reported physiological signaling roles. In spite of their described actions, the chemical/biochemical mechanisms of activity have not been established. From a chemical perspective, it is likely that metals and metalloproteins are possible biological targets for the actions of these species. Thus, the chemical biology of hydrogen sulfide and persulfides with metals and metalloproteins will be discussed as a prelude to future speculation regarding their physiological function and utility.

Section snippets

Hydrogen sulfide: introduction

Recent studies indicate that hydrogen sulfide (H2S) is an important and endogenously generated signaling molecule [1] akin to other small molecule signaling agents such as nitric oxide and carbon monoxide [2]. However, the physiological targets and biochemical mechanisms associated with the biological activity of H2S (and derived species) remain to be established. As a toxic gas, environmental/industrial exposure to supraphysiological levels of H2S can be lethal. However, exposure of mice to

Hydropersulfides and related polysulfides: introduction

Recent reports indicate that hydropersulfides (RSSH) and related polysulfur compounds (RSSnR, n > 1, R = alkyl or H) are highly prevalent in biological systems [32]. RSSH can be formed via the reaction of H2S with a disulfide (RSSR) or a sulfenic acid ((1), (2), respectively) [6,33,34], or via the actions of cystathionine beta-synthase, cystathionine gamma-lyase [35], or mercaptopyruvate sulfur transferase [36]. It has also been recently shown that cysteine hydropersulfide (Cys-SSH) can be made

Conclusions/future directions

It is clear that RSSH have a propensity for reacting with biological metals and metalloproteins. However, the intimate mechanistic details of these interactions and the array of possible biological targets have only begun to be elucidated. There are several biologically relevant and likely interactions that remain to be examined. For example, owing to the chemical properties of Zn2+ (a borderline ‘soft’ metal known to bind readily to thiols), it is possible that RSSH can affect Zn2+ metabolism,

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

Nothing declared.

Acknowledgements

The authors want to acknowledge Takaaki Akaike, Yoshito Kumagai, and Peter Nagy for their helpful discussions regarding this topic.

References (79)

  • J.-P.R. Chauvin et al.

    Hydropersulfides: H-Atom transfer agents par excellence

    J Am Chem Soc

    (2017)
  • R. Millikin et al.

    The chemical biology of protein hydropersulfides: studies of a possible protective function of biological hydropersulfide generation

    Free Rad Biol Med

    (2016)
  • N. Krishnan et al.

    H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response

    Sci Signal

    (2011)
  • R. Greiner et al.

    Polysulfides link H2S to protein thiol oxidation

    Antioxidants Redox Signal

    (2013)
  • N.M.F.S.A. Cerqueira et al.

    Theoretical studies on the mechanisms of some Mo enzymes

    J Biol Inorg Chem

    (2015)
  • U. Zander et al.

    Structural basis for the oxidation of protein-bound sulfur by the sulfur cycle molybdohemo-enzyme sulfane dehydrogenase SoxCD

    J Biol Chem

    (2011)
  • U. Kappler et al.

    The bacterial SoxAX cytochromes

    Cell Mol Life Sci

    (2013)
  • T. Dambe et al.

    Structure of the cytochrome complex SoxXA of Paracoccuc pantotrophus, a heme enzyme initiating chemotrophic sulfur oxidation

    J Struct Biol

    (2005)
  • M. Akiyama et al.

    The capture of cadmium by reactive polysulfides attenuates cadmium-induced adaptive responses and hepatotoxicity

    Chem Res Toxicol

    (2017)
  • H. Kimura

    Physiological roles of hydrogen sulfide and polysulfides

  • J.M. Fukuto et al.

    Small molecule signaling agents: the integrated chemistry and biochemistry of nitrogen oxides, oxides of carbon, dioxygen, hydrogen sulfide and their derived species

    Chem Res Toxicol

    (2012)
  • E. Blackstone et al.

    H2S induces a suspended animation-like state in mice

    Science

    (2005)
  • L.J. Ignarro

    Nitric oxide: a unique endogenous signaling molecule in vascular biology (nobel lecture)

    Angew Chem Int Ed

    (1999)
  • L. Alvarez et al.

    The chemical biology of hydropersulfides and related species: possible roles in cellular protection and redox signaling

    Antioxidants Redox Signal

    (2017)
  • M.R. Filipovic et al.

    Chemical biology of H2S signaling through persulfidation

    Chem Rev

    (2018)
  • V. Vivitsky et al.

    Sulfide oxidation by a noncanonical pathway in red blood cells generates thiosulfate and polysulfides

    J Biol Chem

    (2015)
  • V. Vivitsky et al.

    Cytochrome c reduction by H2S potentiates sulfide signaling

    ACS Chem Biol

    (2018)
  • T. Bostelaar et al.

    Hydrogen sulfide oxidation by myoglobin

    J Am Chem Soc

    (2016)
  • Z. Palinkas et al.

    Interactions of hydrogen sulfide with myeloperoxidase

    Br J Pharmacol

    (2015)
  • J.P. Collman et al.

    Using a functional enzyme model to understand the chemistry behind hydrogen sulfide induced hibernation

    Proc Natl Acad Sci, USA

    (2009)
  • J. Jiang et al.

    Hydrogen sulfide – mechanisms of toxicity and development of an antidote

    Sci Rep

    (2016)
  • C. Szabo et al.

    Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part 1. Biochemical and physiological mechanisms

    Br J Pharmacol

    (2014)
  • B.C. Hill et al.

    Interactions of sulphide and other ligands with cytochrome c oxidase

    Biochem J

    (1984)
  • M.A. Powell et al.

    Hydrogen sulfide oxidation in coupled to oxidative phosphorylation in mitochondria of Solemya reidi

    Science

    (1986)
  • R. Pietri et al.

    Hydrogen sulfide and hemeproteins: knowledge and mysteries

    Antioxidants Redox Signal

    (2011)
  • D.C. Johnson et al.

    Structure, function and formation of biological iron-sulfur clusters

    Annu Rev Biochem

    (2005)
  • H. Beinert

    A tribute to sulfur

    Eur J Biochem

    (2000)
  • R.G. Pearson

    Hard and soft acids and bases, HSAB, Part 1

    J Chem Educ

    (1968)
  • M.G. Mostofa et al.

    Hydrogen sulfide modulates cadmium-induced physiological and biochemical responses to alleviate cadmium toxicity in rice

    Sci Rep

    (2015)
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