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Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism
Journal article   Open access   Peer reviewed

Use of Tissue Metabolite Analysis and Enzyme Kinetics To Discriminate between Alternate Pathways for Hydrogen Sulfide Metabolism

Kristie D Cox Augustyn, Michael R Jackson and Marilyn Schuman Jorns
Biochemistry (Easton), v 56(7), pp 986-996
21 Feb 2017
DOI: https://doi.org/10.1021/acs.biochem.6b01093
PMID: 28107627
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc6366607View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Anaerobiosis Animals Cysteine - metabolism Glutathione - metabolism Hydrogen Sulfide - metabolism Kinetics Liver - metabolism Male Metabolic Networks and Pathways Myocardium - metabolism Quinone Reductases - chemistry Quinone Reductases - metabolism Rats, Wistar Sulfites - metabolism Ubiquinone - metabolism
Hydrogen sulfide (H S) is an endogenously synthesized signaling molecule that is enzymatically metabolized in mitochondria. The metabolism of H S maintains optimal concentrations of the gasotransmitter and produces sulfane sulfur (S )-containing metabolites that may be functionally important in signaling. Sulfide:quinone oxidoreductase (SQOR) catalyzes the initial two-electron oxidation of H S to S using coenzyme Q as the electron acceptor in a reaction that requires a third substrate to act as the acceptor of S . 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 H S by SQOR with glutathione as the S acceptor 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 H S by SQOR at physiological concentrations of different S acceptors. The results show that the reaction with sulfite as the S acceptor is a major pathway in liver and heart and provide insight into the potential dynamics of H S metabolism.

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31 citations in Web of Science
30 citations in Scopus

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#3 Good Health and Well-Being

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Web of Science research areas
Biochemistry & Molecular Biology
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