Dick Jeffrey M
Wattanothaipayap School, Chiang Mai, Thailand.
PeerJ. 2017 Jun 6;5:e3421. doi: 10.7717/peerj.3421. eCollection 2017.
The changes of protein expression that are monitored in proteomic experiments are a type of biological transformation that also involves changes in chemical composition. Accompanying the myriad molecular-level interactions that underlie any proteomic transformation, there is an overall thermodynamic potential that is sensitive to microenvironmental conditions, including local oxidation and hydration potential. Here, up- and down-expressed proteins identified in 71 comparative proteomics studies were analyzed using the average oxidation state of carbon () and water demand per residue ([Formula: see text]), calculated using elemental abundances and stoichiometric reactions to form proteins from basis species. Experimental lowering of oxygen availability (hypoxia) or water activity (hyperosmotic stress) generally results in decreased or [Formula: see text] of up-expressed compared to down-expressed proteins. This correspondence of chemical composition with experimental conditions provides evidence for attraction of the proteomes to a low-energy state. An opposite compositional change, toward higher average oxidation or hydration state, is found for proteomic transformations in colorectal and pancreatic cancer, and in two experiments for adipose-derived stem cells. Calculations of chemical affinity were used to estimate the thermodynamic potentials for proteomic transformations as a function of fugacity of O and activity of HO, which serve as scales of oxidation and hydration potential. Diagrams summarizing the relative potential for formation of up- and down-expressed proteins have predicted equipotential lines that cluster around particular values of oxygen fugacity and water activity for similar datasets. The changes in chemical composition of proteomes are likely linked with reactions among other cellular molecules. A redox balance calculation indicates that an increase in the lipid to protein ratio in cancer cells by 20% over hypoxic cells would generate a large enough electron sink for oxidation of the cancer proteomes. The datasets and computer code used here are made available in a new R package, .
蛋白质组学实验中监测到的蛋白质表达变化是一种生物转化类型，它也涉及化学成分的变化。伴随着任何蛋白质组转化背后的无数分子水平相互作用，存在着一种对微环境条件敏感的整体热力学势，包括局部氧化和水合势。在这里，使用碳（）的平均氧化态和每个残基的需水量（[公式：见正文]）对71项比较蛋白质组学研究中鉴定出的上调和下调表达的蛋白质进行了分析，该平均氧化态和需水量通过元素丰度和从基础物种形成蛋白质的化学计量反应来计算。与下调表达的蛋白质相比，实验性降低氧可用性（缺氧）或水活性（高渗应激）通常会导致上调表达蛋白质的降低或[公式：见正文]降低。化学成分与实验条件的这种对应关系为蛋白质组向低能状态的吸引提供了证据。在结直肠癌和胰腺癌以及两项脂肪来源干细胞实验中，蛋白质组转化发现了朝着更高平均氧化或水合状态相反的组成变化。化学亲和力计算用于估计蛋白质组转化的热力学势作为O逸度和H₂O活性的函数，O逸度和H₂O活性用作氧化和水合势的尺度。总结上调和下调表达蛋白质形成相对势的图表预测了等势线，这些等势线围绕相似数据集的特定氧逸度和水活性值聚集。蛋白质组化学成分的变化可能与其他细胞分子之间的反应有关。氧化还原平衡计算表明，癌细胞中脂质与蛋白质的比例比缺氧细胞增加20%将产生足够大的电子阱用于癌细胞蛋白质组的氧化。这里使用的数据集和计算机代码在一个新的R包中提供。
