Hadler H I, Cook G L
J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):601-12.
Sulfate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxybutyrate is the substrate. A high level of sulfate in the absence of added phosphate induces a pseudo state three of the mitochondria. Uncoupling is inhibited by rutamycin. Thus sulfate is activated by the mechanism usually utilized by phosphate, and the target for hydrazine is the bond holding electrophilic sulfate. ATP, ADP, PPi, and Mg++ protect against hydrazine, presumably by causing a conformational change of the phosphorylating enzymes which participate in oxidative phosphorylation. Arsenate also could substitute for phosphate in the transitory uncoupling induced by hydrazine. Uncoupling is again inhibited by rutamycin; thus arsenate is also activated by the enzymic mechanism usually utilized by phosphate. Since sulfate is known to enhance the carcinogenicity of certain carcinogens, these results expand the experimental confluence between oxidative phosphorylation and chemical carcinogenesis and also serve to explain at least in part the "toxic" effects of sulfate. Because of the analogous results with arsenate and sulfate, it is suggested that arsenate, like sulfate, may enhance the carcinogenicity of other carcinogens. The data are compatible with epidemiological studies which implicate some role in carcinogenesis for sulfate (often measured as a sulfur dioxide equivalent) and arsenate.
当以β-羟基丁酸作为底物时，在肼诱导的大鼠肝线粒体短暂解偶联过程中，硫酸盐可替代磷酸盐。在不添加磷酸盐的情况下，高浓度的硫酸盐会诱导线粒体进入假状态3。解偶联受到鱼藤霉素的抑制。因此，硫酸盐是通过通常由磷酸盐利用的机制被激活的，而肼的作用靶点是连接亲电子硫酸盐的键。ATP、ADP、焦磷酸和镁离子可防止肼的作用，推测是通过引起参与氧化磷酸化的磷酸化酶的构象变化来实现的。砷酸盐在肼诱导的短暂解偶联中也能替代磷酸盐。解偶联同样受到鱼藤霉素的抑制；因此，砷酸盐也是通过通常由磷酸盐利用的酶促机制被激活的。由于已知硫酸盐会增强某些致癌物的致癌性，这些结果扩展了氧化磷酸化与化学致癌作用之间的实验交汇点，并且至少部分地解释了硫酸盐的“毒性”作用。鉴于砷酸盐和硫酸盐有类似的结果，有人提出砷酸盐可能像硫酸盐一样，会增强其他致癌物的致癌性。这些数据与流行病学研究结果相符，这些研究表明硫酸盐（通常以二氧化硫当量来衡量）和砷酸盐在致癌过程中起到了一定作用。
