Figure 1.

Generation of thiosulfate from H₂S in the mitochondrial sulfide oxidation pathways. Hydrogen sulfide (H₂S) is produced by enzymes cystathione γ-lyase (CSE) and cystathionine β-synthase (CBS) in the trans-sulfuration pathway. A third enzyme, 3-mercaptopyruvate sulfurtransferase (MST), also produces endogenous H₂S in the presence of the substrate 3-mercaptopyruvate. A membrane-bound sulfide, quinone oxidoreductase (SQR), oxidizes H₂S to persulfide, which is transferred to a glutathione (GSH). A persulfide dioxygenase (PDO) in the mitochondrial matrix oxides one glutathione persulfide (GSSH) to sulfite (H₂SO₃), which is then used in a sulfurtransferase reaction catalyzed by the enzyme rhodanase (Rhd) to form thiosulfate (S₂O₃²⁻) by transferring a second glutathione persulfide from SQR to sulfite. Sulfite can be further oxidized by sulfite oxidase (SO) to form sulfate (SO₄²⁻) and is subsequently excreted in urine. PDO and SO are oxygen dependent enzymes.