Moosmann Bernd, Hajieva Parvana
Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
Institute for Translational Medicine, MSH Medical School Hamburg, 20457 Hamburg, Germany.
Antioxidants (Basel). 2022 Apr 29;11(5):885. doi: 10.3390/antiox11050885.
Thiyl radicals are exceptionally interesting reactive sulfur species (RSS), but rather rarely considered in a biological or medical context. We here review the reactivity of protein thiyl radicals in aqueous and lipid phases and provide an overview of their most relevant reaction partners in biological systems. We deduce that polyunsaturated fatty acids (PUFAs) are their preferred reaction substrates in lipid phases, whereas protein side chains arguably prevail in aqueous phases. In both cellular compartments, a single, dominating thiyl radical-specific antioxidant does not seem to exist. This conclusion is rationalized by the high reaction rate constants of thiyl radicals with several highly concentrated substrates in the cell, precluding effective interception by antioxidants, especially in lipid bilayers. The intractable reactivity of thiyl radicals may account for a series of long-standing, but still startling biochemical observations surrounding the amino acid cysteine: (i) its global underrepresentation on protein surfaces, (ii) its selective avoidance in aerobic lipid bilayers, especially the inner mitochondrial membrane, (iii) the inverse correlation between cysteine usage and longevity in animals, (iv) the mitochondrial synthesis and translational incorporation of cysteine persulfide, and potentially (v) the ex post introduction of selenocysteine into the genetic code.
硫自由基是一类极其有趣的活性硫物种（RSS），但在生物学或医学背景下却很少被考虑。我们在此综述了蛋白质硫自由基在水相和脂质相中的反应活性，并概述了它们在生物系统中最相关的反应伙伴。我们推断，多不饱和脂肪酸（PUFA）是它们在脂质相中的首选反应底物，而在水相中，蛋白质侧链可能占主导地位。在这两个细胞区室中，似乎不存在单一的、占主导地位的硫自由基特异性抗氧化剂。这一结论的合理性在于硫自由基与细胞中几种高浓度底物的反应速率常数很高，使得抗氧化剂难以有效拦截，尤其是在脂质双层中。硫自由基难以捉摸的反应活性可能解释了围绕氨基酸半胱氨酸的一系列长期存在但仍令人惊讶的生化现象：（i）其在蛋白质表面普遍含量较低；（ii）在有氧脂质双层中，尤其是线粒体内膜中，它被选择性避开；（iii）动物体内半胱氨酸使用情况与寿命之间的负相关；（iv）半胱氨酸过硫化物的线粒体合成及翻译掺入，以及可能的（v）硒代半胱氨酸事后引入遗传密码。
