Stadtman E R, Berlett B S
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0342, USA.
Drug Metab Rev. 1998 May;30(2):225-43. doi: 10.3109/03602539808996310.
Highly reactive oxygen species that are formed during normal metabolism and under conditions of oxidative stress are able to oxidize proteins or convert lipid and carbohydrate derivatives to compounds that react with functional groups on proteins. Among other changes, these ROS-mediated reactions lead to the formation of protein carbonyl derivatives, which serves as a marker of ROS-mediated protein damage. On the basis of this marker, it is established that oxidatively damaged protein is associated with aging and some diseases. The accumulation of oxidatively damaged protein reflects the balance among a myriad of factors that govern the rates of ROS generation and the rate at which damaged protein is degraded. Peroxynitrite, which is formed under normal physiological conditions, is able to oxidize methionine residues in proteins and to nitrate tyrosine residues; however, its ability to do so is dependent on the availability of CO2, which stimulates the nitration of tyrosine residues but inhibits the oxidation of methionine residues. Nitration of tyrosine residues may contribute to peroxynitrite toxicity, as nitration precludes the phosphorylation or nucleotidylation of tyrosine residues and thereby seriously compromises one of the most important mechanisms of cellular regulation and signal transduction.
在正常新陈代谢以及氧化应激条件下形成的高活性氧物种能够氧化蛋白质，或将脂质和碳水化合物衍生物转化为可与蛋白质上的官能团发生反应的化合物。除其他变化外，这些由活性氧介导的反应会导致蛋白质羰基衍生物的形成，该衍生物可作为活性氧介导的蛋白质损伤的标志物。基于这一标志物，已证实氧化损伤的蛋白质与衰老及某些疾病相关。氧化损伤蛋白质的积累反映了众多因素之间的平衡，这些因素决定了活性氧的生成速率以及受损蛋白质的降解速率。在正常生理条件下形成的过氧亚硝酸根能够氧化蛋白质中的甲硫氨酸残基并使酪氨酸残基硝化；然而，其这样做的能力取决于二氧化碳的可用性，二氧化碳会刺激酪氨酸残基的硝化，但会抑制甲硫氨酸残基的氧化。酪氨酸残基的硝化可能会导致过氧亚硝酸根毒性，因为硝化会阻止酪氨酸残基的磷酸化或核苷酸化，从而严重损害细胞调节和信号转导这一最重要的机制之一。
