Title:
Cysteine persulfides and polysulfides: formation, metabolisms and unique antioxidant activities

Tomohiro Sawa
Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University

Abstract:
　Hydropolysulfides such as cysteine persulfide (Cys-SSH) have been proposed to occur in biological systems.  Examples include cysteine residues in certain enzymes such as sulfide:quinone oxidoreductase, persulfide dioxygenase, rhodanese (thiosulfate sulfurtransferase), mercaptopyruvate sulfurtransferase, and during enzymatic degradation of cystine catalyzed by g-cystathionase to produce Cys-SSH.  It has been hypothesized that sulfide moieties may transfer from one to the other acceptor of high-molecular weight (protein, enzyme) and low-molecular weight substance (cysteine, glutathione [GSH]).  However, exact molecular identities, biological levels, as well as biological properties of polysulfides remain largely unknown.  We have recently developed the mass spectrometry-based analytical method for quantitative identification of an array of polysulfides in biological samples.  According to this newly developed method, we could identify for the first time endogenous formation of a variety of polysulfides, e.g, persulfide forms of cysteine (Cys-SSH), homocysteine (Hcys-SSH), and GSH (GSSH), as well as hydropolysulfide and oxidized forms (RS-SnH and RS-Sn-SR, n > 2).  In fact, appreciable amounts of these polysulfides were found in mouse specimens and human plasma.  Mouse study revealed that organ distribution of polysulfides showed different profiles in different organs such as heart, liver, plasma, brain and lung, suggesting the different metabolic regulation of polysulfides in those organs.  These data may be suggestive of the importance of complex metabolome of polysulfides in biological system, which may then promote further understanding of polysulfide metabolome and may shed light on a new era of the unique sulfur biology.  In this seminar, unique antioxidant properties of cysteine persulfides will also be discussed.

References:
Ida, T., et al. Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proc. Natl. Acad. Sci. USA, 111, 7606-7611 (2014).