The essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. The aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. This observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. This study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.

中文翻译：

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通过五种生物标志物测定健康女性血清中的铜状态

必需的微量元素铜与许多重要的生理过程相关。疾病可能导致铜稳态的变化并影响人类健康。通过合适的生物标志物对铜状态进行可靠评估可以快速检测铜代谢的细微变化。为此，除了血清铜和铜蓝蛋白 (CP) 浓度之外，还需要其他生物标志物。本研究的目的是调查健康女性血清中新兴的铜生物标志物 CP 氧化酶 (CPO) 活性、可交换铜 (CuEXC) 和不稳定铜，并将其与传统生物标志物总血清铜和 CP 进行比较。这项观察性研究测定了 110 名健康女性血清中的 CPO 活性、非 CP 结合铜物种 CuEXC 和不稳定铜、血清总铜和 CP。在 24 周内的四个时间点采集样本。血清总铜和CP浓度均在参考范围内。所有五种生物标志物的比较可以深入了解它们的关系、个体内和个体间的变异性以及年龄依赖性。相关性和主成分分析（PCA）表明，CP、CPO 活性和总铜相关性良好，其次是 CuEXC，而不稳定铜池与其他参数无关。这项研究表明，非 CP 结合铜物种代表了与总铜或 CP 结合铜受到不同调节的铜池，使它们成为有趣的补充生物标志物，能够更全面地评估身体铜状态，并具有潜在的临床应用相关性。