Human Sulfide:Quinone
Oxidoreductase Catalyzes the
First Step in Hydrogen Sulfide Metabolism and Produces a Sulfane Sulfur
Metabolite
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Abstract
Sulfide:quinone oxidoreductase (SQOR) is a membrane-bound
enzyme
that catalyzes the first step in the mitochondrial metabolism of H<sub>2</sub>S. Human SQOR is successfully expressed at low temperature
in <i>Escherichia coli</i> by using an optimized synthetic
gene and cold-adapted chaperonins. Recombinant SQOR contains noncovalently
bound FAD and catalyzes the two-electron oxidation of H<sub>2</sub>S to S<sup>0</sup> (sulfane sulfur) using CoQ<sub>1</sub> as an electron
acceptor. The prosthetic group is reduced upon anaerobic addition
of H<sub>2</sub>S in a reaction that proceeds via a long-wavelength-absorbing
intermediate (λ<sub>max</sub> = 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 (H<sub>2</sub>S<sub>2</sub>), respectively. Importantly,
thiosulfate is a known intermediate in the oxidation of H<sub>2</sub>S by intact animals and the major product formed in glutathione-depleted
cells or mitochondria. Oxidation of H<sub>2</sub>S by SQOR with sulfite
as the sulfane sulfur acceptor is rapid and highly efficient at physiological
pH (<i>k</i><sub>cat</sub>/<i>K</i><sub>m,H<sub>2</sub>S</sub> = 2.9 × 10<sup>7</sup> M<sup>–1</sup> s<sup>–1</sup>). 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
H<sub>2</sub>S oxidation by mammalian tissues