title: Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism.
abstract: Hydrogen sulfide (H2S) is an endogenously synthesized signaling molecule that is enzymatically metabolized in mitochondria. The metabolism of H2S maintains optimal concentrations of the gasotransmitter and produces sulfane sulfur (S0)-containing metabolites that may be functionally important in signaling. Sulfide:quinone oxidoreductase (SQOR) catalyzes the initial two-electron oxidation of H2S to S0using coenzyme Q as the electron acceptor in a reaction that requires a third substrate to act as the acceptor of S0. We discovered that sulfite is a highly efficient acceptor and proposed that sulfite is the physiological acceptor in a reaction that produces thiosulfate, a known metabolic intermediate. This model has been challenged by others who assume that the intracellular concentration of sulfite is very low, a scenario postulated to favor reaction of SQOR with a considerably poorer acceptor, glutathione. In this study, we measured the intracellular concentration of sulfite and other metabolites in mammalian tissues. The values observed for sulfite in rat liver (9.2 μM) and heart (38 μM) are orders of magnitude higher than previously assumed. We discovered that the apparent kinetics of oxidation of H2S by SQOR with glutathione as the S0acceptor reflect contributions from other SQOR-catalyzed reactions, including a novel glutathione:CoQ reductase reaction. We used observed metabolite levels and steady-state kinetic parameters to simulate rates of oxidation of H2S by SQOR at physiological concentrations of different S0acceptors. The results show that the reaction with sulfite as the S0acceptor is a major pathway in liver and heart and provide insight into the potential dynamics of H2S metabolism.
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
authors.forename: Kristie D Cox
authors.initials: KD
authors.lastname: Augustyn
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jackson
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , Philadelphia, Pennsylvania 19102, United States.
authors.forename: Marilyn Schuman
authors.identifier: 0000-0003-2867-0287
authors.initials: MS
authors.lastname: Jorns
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D009206:Myocardium / Q000378:metabolism*; D011808:Quinone Reductases / Q000737:chemistry / Q000378:metabolism*; D017208:Rats, Wistar; D013447:Sulfites / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D013447:Sulfites; D014451:Ubiquinone; D011808:Quinone Reductases; C073412:sulfide quinone reductase; D005978:Glutathione; D003545:Cysteine; D006862:Hydrogen Sulfide