Human Sulfide:Quinone Oxidoreductase Catalyzes the First Step in Hydrogen Sulfide Metabolism and Produces a Sulfane Sulfur Metabolite
Human Sulfide:Quinone Oxidoreductase Catalyzes the First Step in Hydrogen Sulfide Metabolism and Produces a Sulfane Sulfur Metabolite
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DOI：
10.1021/bi300778t
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发表时间：
2012-08-28
期刊：
影响因子：
2.9
通讯作者：
Jorns, Marilyn Schuman
中科院分区：
文献类型：
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作者：
Jackson, Michael R.;Melideo, Scott L.;Jorns, Marilyn Schuman
硫化物：醌氧化还原酶（SQOR）是一种膜结合酶，催化H2S线粒体代谢的第一步。利用优化的合成基因和冷适应伴侣蛋白，在大肠杆菌中成功地在低温下表达了人SQOR。重组SQOR含有非共价结合的FAD，并使用CoQ作为电子受体催化H2S至S-0（硫烷硫）的双电子氧化。辅基在厌氧添加H2S的反应中被还原，该反应通过长波长吸收中间体（λ（max）= 673 nm）进行。氰化物、亚硫酸盐或硫化物可在反应中充当硫烷硫受体，所述反应（i）分别在8.5、7.5或7.0显示最佳pH，和（ii）分别产生硫氰酸盐、硫代硫酸盐或过氧化氢（H2 S2）的推定硫类似物。重要的是，硫代硫酸盐是完整动物氧化H2S的已知中间体，也是谷胱甘肽耗尽细胞或线粒体中形成的主要产物。以亚硫酸盐作为硫烷硫受体，通过SQOR氧化H2S在生理pH下快速且高效（k（cat）/K-m，K-H2S = 2.9 x 10（7）M-1 s（-1））。在pH 8.5下用氰化物（一种明显的人工受体）观察到类似的效率，而在pH 7.0下用硫化物作为受体观察到低100倍的值。后一种反应不太可能发生在健康个体中，但在某些病理条件下可能变得显著。我们建议，亚硫酸盐是生理受体的硫烷硫和SQOR反应是H2S氧化过程中产生的哺乳动物组织的硫代硫酸盐的主要来源。
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 S-0 (sulfane sulfur) using CoQ, 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 (lambda(max) = 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 (k(cat)/K-m,K-H2S = 2.9 x 10(7) 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.