The Mechanism of the L-Cystine Cleavage Reaction Catalyzed by Rat Liver γ-Cystathionase1

Yamanishi, Tomoko; Tuboi, Syozo

doi:10.1093/oxfordjournals.jbchem.a133393

Cited by 75 publications

(45 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1A and SI Appendix, Fig. S3C) (8). Recombinant CBS also catalyzed generation of primarily CysSSH from CysSSCys (Fig.…”

Section: Significancementioning

confidence: 92%

“…S3A). If cystine (CysSSCys) is used as a substrate for CSE instead of cystathionine, CSE may generate Cys hydropersulfide (CysSSH) as an unstable intermediate (8). However, the physicochemical nature and biological relevance of CysSSH remain unclear.…”

Section: Significancementioning

confidence: 99%

“…Our laboratory recently showed that the presence of hydrogen sulfide anion (HS − ) may be responsible for the regulation and metabolism of various important electrophilic species [e.g., 8-nitroguanosine 3′,5′-cyclic GMP (8-nitro-cGMP)] (2). However, these studies also indicated that reactive intermediates other than HS − likely react with the electrophiles of interest.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling

Ida¹,

Sawa

Ihara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

811

1,236

View full text Add to dashboard Cite

Using methodology developed herein, it is found that reactive persulfides and polysulfides are formed endogenously from both small molecule species and proteins in high amounts in mammalian cells and tissues. These reactive sulfur species were biosynthesized by two major sulfurtransferases: cystathionine β-synthase and cystathionine γ-lyase. Quantitation of these species indicates that high concentrations of glutathione persulfide (perhydropersulfide >100 μM) and other cysteine persulfide and polysulfide derivatives in peptides/proteins were endogenously produced and maintained in the plasma, cells, and tissues of mammals (rodent and human). It is expected that persulfides are especially nucleophilic and reducing. This view was found to be the case, because they quickly react with H 2 O 2 and a recently described biologically generated electrophile 8-nitroguanosine 3′,5′-cyclic monophosphate. These results indicate that persulfides are potentially important signaling/effector species, and because H 2 S can be generated from persulfide degradation, much of the reported biological activity associated with H 2 S may actually be that of persulfides. That is, H 2 S may act primarily as a marker for the biologically active of persulfide species.thiol redox | hydrogen sulfide | electrophilic signaling | polysulfidomics H ydrogen sulfide (H 2 S) has been suggested to be an endogenous small molecule signaling species (1) by unknown mechanisms. Our laboratory recently showed that the presence of hydrogen sulfide anion (HS − ) may be responsible for the regulation and metabolism of various important electrophilic species [e.g., 8-nitroguanosine 3′,5′-cyclic GMP (8-nitro-cGMP)] (2). However, these studies also indicated that reactive intermediates other than HS − likely react with the electrophiles of interest. These previous studies alluded to the generation of a more reactive sulfur species capable of reacting with electrophiles, such as 8-nitro-cGMP. As reported herein, it was determined that reactive sulfur intermediates, such as hydropersulfides (RSSH) and polysulfides [RS(S) n H and RS(S) n SR], are formed in appreciable amounts during sulfur amino acid metabolism and possess important chemical and biological properties. Some of these sulfide species have long been known as sulfane sulfur compounds, which were suggested to exist endogenously in mammalian systems (1,(3)(4)(5). Reports also indicated that a hydropersulfide moiety with the general molecular formula RSSH may be formed on specific protein cysteine (Cys) residues, most typically of sulfur-transferring enzymes (i.e., sulfurtransferases) during enzymatic reactions (1, 5). Although such persulfide chemical reactivity is thought to be involved in the catalytic activity of particular enzymes (e.g., rhodanese, Cys desulfurases, and sulfide:quinone oxidoreductase) (6, 7), the more general physiological function and occurrence of Cys persulfides (CysSSH) and related species in cells and tissues, especially mammals, were unclear. Moreover, the exact chemical nature ...

show abstract

“…1A and SI Appendix, Fig. S3C) (8). Recombinant CBS also catalyzed generation of primarily CysSSH from CysSSCys (Fig.…”

Section: Significancementioning

confidence: 92%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling

Ida¹,

Sawa

Ihara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

811

1,236

View full text Add to dashboard Cite

show abstract

“…As the cystine elimination reaction also proceeded linearly with respect to incubation time under the conditions employed, the thiocysteine produced would not have been cleaved by the enzyme to produce a second pyruvate. It would also be impossible for the enzyme to produce sulˆde from thiocysteine through a mechanism supported by a disulˆde as reported for rat liver CTT g-lyase, 24) because the S. cerevisiae enzyme has no disulˆde in its molecule. 8) Determination of the absorption spectrum of the enzyme was carried out under the same conditions as those in Fig.…”

Section: The Internal Schiš Base (O)mentioning

confidence: 94%

Substrate Inhibition ofL-Cysteine α,β-Elimination Reaction Catalyzed byL-Cystathionine γ-Lyase ofSaccharomyces cerevisiae

Yamagata

Isaji

Yamane

et al. 2002

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

“…Current knowledge about sulfur donors assumes that the primary source of sulfane sulfur in eukaryotes relies on L-cysteine desulfuration pathway (9). It has been demonstrated that rat liver cystathionase (EC 4.4.1.1) greatly enhances the trans-sulfuration of cyanide to thiocyanate; thus, a product of the cystathionase reaction, thiocystine, has been suggested to serve as the sulfur donor substrate for rhodanese (10).…”

Section: [F/y]-x 3 -H-[l/i/v]-p-g-a-x 2 -[L/i/v/f]) and At The C-termmentioning

confidence: 99%

Common themes and variations in the rhodanese superfamily

2007

View full text Add to dashboard Cite

SummaryThe rhodanese homology domain is a ubiquitous fold found in several phylogenetically related proteins encoded by eubacterial, archeal, and eukaryotic genomes. Although rhodanese-like proteins share evolutionary relationships, analysis of their sequences highlights that they are so heterogeneous to form the rhodanese superfamily. The variability occurs at different levels including sequence, active site loop length, presence of a critical catalytic Cys residue, and domain arrangement. Even within the same genome, multiple genes encode rhodanese-like proteins presenting with variably arranged rhodanese domain(s): as single or tandem domain(s), or combined with other protein domain(s). Given the highly variable organization of the rhodanese domain(s) and the context where it is found, here we review the structural organization and function of the rhodanese-like proteins. The overview of the most recent findings about rhodanese allow us to depict a superfamily of versatile proteins relying on persulfide chemistry to accomplish cellular functions spanning from resistance to environmental threats, such as cyanide, and key cellular reactions related to sulfur metabolism and progression of cell cycle. IUBMB Life, 59: 51-59, 2007

show abstract

The Mechanism of the L-Cystine Cleavage Reaction Catalyzed by Rat Liver γ-Cystathionase1

Cited by 75 publications

References 0 publications

Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling

Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling

Substrate Inhibition ofL-Cysteine α,β-Elimination Reaction Catalyzed byL-Cystathionine γ-Lyase ofSaccharomyces cerevisiae

Common themes and variations in the rhodanese superfamily

Contact Info

Product

Resources

About