Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA; Department of Microbiology & Immunology, Montana State University, Bozeman, MT 59717, USA.
Division of Biochemistry, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, SE 171 77 Stockholm, Sweden.
Free Radic Biol Med. 2018 Nov 1;127:248-261. doi: 10.1016/j.freeradbiomed.2018.03.051. Epub 2018 Mar 30.
Over the past seven decades, research on autotrophic and heterotrophic model organisms has defined how the flow of electrons ("reducing power") from high-energy inorganic sources, through biological systems, to low-energy inorganic products like water, powers all of Life's processes. Universally, an initial major biological recipient of these electrons is nicotinamide adenine dinucleotide-phosphate, which thereby transits from an oxidized state (NADP) to a reduced state (NADPH). A portion of this reducing power is then distributed via the cellular NADPH-dependent disulfide reductase systems as sequential reductions of disulfide bonds. Along the disulfide reduction pathways, some enzymes have active sites that use the selenium-containing amino acid, selenocysteine, in place of the common but less reactive sulfur-containing cysteine. In particular, the mammalian/metazoan thioredoxin systems are usually selenium-dependent as, across metazoan phyla, most thioredoxin reductases are selenoproteins. Among the roles of the NADPH-dependent disulfide reductase systems, the most universal is that they provide the reducing power for the production of DNA precursors by ribonucleotide reductase (RNR). Some studies, however, have uncovered examples of NADPH-independent disulfide reductase systems that can also support RNR. These systems are summarized here and their implications are discussed.
在过去的七十年中，对自养和异养模式生物的研究定义了电子（“还原力”）如何从高能无机源通过生物系统流向低能无机产物，如水中，从而为所有生命过程提供动力。普遍来说，这些电子的最初主要生物受体是烟酰胺腺嘌呤二核苷酸磷酸（NADP），它由此从氧化态（NADP）转变为还原态（NADPH）。然后，一部分还原力通过细胞 NADPH 依赖性二硫键还原酶系统分配，作为二硫键的连续还原。在二硫键还原途径中，一些酶的活性位点使用含硒的氨基酸硒代半胱氨酸代替常见但反应性较弱的含硫半胱氨酸。特别是，哺乳动物/后生动物硫氧还蛋白系统通常依赖硒，因为在整个后生动物门中，大多数硫氧还蛋白还原酶都是硒蛋白。在 NADPH 依赖性二硫键还原酶系统的众多作用中，最普遍的作用是为核糖核苷酸还原酶 (RNR) 生成 DNA 前体提供还原力。然而，一些研究发现了 NADPH 独立的二硫键还原酶系统也可以支持 RNR 的例子。这里总结了这些系统，并讨论了它们的意义。
