Main content area

Human Sulfide:Quinone Oxidoreductase Catalyzes the First Step in Hydrogen Sulfide Metabolism and Produces a Sulfane Sulfur Metabolite

Jackson, Michael R., Melideo, Scott L., Jorns, Marilyn Schuman
Biochemistry 2012 v.51 no.34 pp. 6804-6815
Escherichia coli, chaperonins, cyanides, humans, hydrogen peroxide, hydrogen sulfide, metabolism, metabolites, mitochondria, oxidation, pH, sulfur, synthetic genes, temperature, thiosulfates, tissues
Sulfide:quinone oxidoreductase (SQOR) is a membrane-bound enzyme that catalyzes the first step in the mitochondrial metabolism of H₂S. Human SQOR is successfully expressed at low temperature in Escherichia coli by using an optimized synthetic gene and cold-adapted chaperonins. Recombinant SQOR contains noncovalently bound FAD and catalyzes the two-electron oxidation of H₂S to S⁰ (sulfane sulfur) using CoQ₁ as an electron acceptor. The prosthetic group is reduced upon anaerobic addition of H₂S in a reaction that proceeds via a long-wavelength-absorbing intermediate (λₘₐₓ = 673 nm). Cyanide, sulfite, or sulfide can act as the sulfane sulfur acceptor in reactions that (i) exhibit pH optima at 8.5, 7.5, or 7.0, respectively, and (ii) produce thiocyanate, thiosulfate, or a putative sulfur analogue of hydrogen peroxide (H₂S₂), respectively. Importantly, thiosulfate is a known intermediate in the oxidation of H₂S by intact animals and the major product formed in glutathione-depleted cells or mitochondria. Oxidation of H₂S by SQOR with sulfite as the sulfane sulfur acceptor is rapid and highly efficient at physiological pH (kcₐₜ/Kₘ,H₂S = 2.9 × 10⁷ M–¹ s–¹). A similar efficiency is observed with cyanide, a clearly artificial acceptor, at pH 8.5, whereas a 100-fold lower value is seen with sulfide as the acceptor at pH 7.0. The latter reaction is unlikely to occur in healthy individuals but may become significant under certain pathological conditions. We propose that sulfite is the physiological acceptor of the sulfane sulfur and that the SQOR reaction is the predominant source of the thiosulfate produced during H₂S oxidation by mammalian tissues.