What question did this study set out to answer?

The aim is to provide mechanistic insights into enzymes that generate persulfides and polysulfides and discuss their inhibitors.

February 12, 2026Open Access

Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors

Puntos clave

The aim is to provide mechanistic insights into enzymes that generate persulfides and polysulfides and discuss their inhibitors.
Comprehensive overview of key enzymes involved in persulfide and polysulfide production.
Analysis of the reaction mechanisms of Cystathionine β-synthase, Cystathionine γ-lyase, and others.
Examination of selective inhibitors targeting these enzymes.
Identified key enzymes that mediate production of persulfides and polysulfides.
Highlighted the role of mitochondrial enzymes in the regulation of intracellular levels of reactive sulfur species.
Proposed therapeutic potential of selective inhibitors for elucidating the functions of reactive sulfur species.

Resumen

Reactive sulfur species (RSS), which include various persulfides and polysulfides, are generated by multiple enzymes in vivo and play critical roles in mammalian physiological processes such as redox signaling, metabolic regulation, radical scavenging and anti-inflammatory responses. Cystathionine β -synthase (CBS), cystathionine γ -lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) are well known to mediate endogenous production of hydrogen sulfide (H 2 S), and, together with the mitochondrial isoform of cysteinyl-tRNA synthetase (CARS2), are proposed to be major sources of intracellular persulfides and polysulfides. In mitochondria, enzymes involved in the sulfide oxidation pathway, including sulfide:quinone oxidoreductase (SQOR), persulfide dioxygenase (ETHE1) and thiosulfate sulfurtransferase (TST), also contribute to maintaining and regulating intracellular persulfide levels. Selective inhibitors targeting these enzymes are expected to be powerful tools for elucidating the functions of RSS, as well as having therapeutic potential. In this review, we present a comprehensive overview of these enzymes, focusing on their reaction mechanisms and inhibitors.

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