Use of mathematical modeling to study copper metabolism in humans
Use of mathematical modeling to study copper metabolism in humans
复制标题
DOI：
10.1093/ajcn/81.4.807
复制
发表时间：
2005-04-01
影响因子：
7.1
通讯作者：
Fairweather-Tait, SJ
中科院分区：
文献类型：
--
作者：
Harvey, LJ;Dainty, JR;Fairweather-Tait, SJ
背景：需要提高对铜代谢的理解，以得出更精确的饮食需求估计。目的：验证一种估算内源性铜损失的方法，测试一个简单的模型是否可以预测血浆中标记铜的真实吸收，并利用稳定同位素建立铜代谢的室室模型。设计:铜的稳定同位素是静脉注射到6人,并收集粪便样本14 d。4周后这项研究是重复,但口服剂量,和血液样本为7 d和收集粪便样本14 d.Results:没有显著差异(P = 0.48)估计内源性损失的计算使用铜排泄静脉注射剂量((x) /酒吧+ / - SD: 32 + / - 5%)或吸收和排泄的口服剂量(35 + / - 2%)。一个简单的数学模型拟合等离子体同位素外观数据，估计真实吸收率为8 +/- 2%，而粪便监测测量的吸收率为48-49%。一个更复杂的区室模型预测，当新吸收的铜首次进入血液时，74%被肝脏清除，99%与血浆中的铜蓝蛋白结合。铜的可交换池估计为43 +/- 30 mg。预计每日内源性损失为2.4毫克。结论：结果表明，粪便监测是唯一可以可靠地测量标记铜吸收的方法，并且没有必要通过静脉给药来估计内源性铜损失。区室模型为人类铜代谢提供了新的见解。
Background: An improved understanding of copper metabolism is needed to derive more precise estimates of dietary requirements.Objectives: The objectives were to validate a method for estimating endogenous losses of copper, test whether a simple model can predict true absorption from the plasma appearance of labeled copper, and develop a compartmental model for copper metabolism by using stable isotopes.Design: A stable isotope of copper was intravenously administered to 6 men, and fecal samples were collected for 14 d. Four weeks later the study was repeated, but with an oral dose, and blood samples were collected for 7 d and fecal samples for 14 d.Results: There was no significant difference (P = 0.48) in the estimated endogenous loss of copper calculated by using either the excreted intravenous dose ((x) over bar +/- SD: 32 +/- 5%) or the absorbed and excreted oral dose (35 +/- 2%). A simple mathematical model fitted to plasma isotope appearance data estimated true absorption to be 8 +/- 2% compared with 48-49% measured by fecal monitoring. A more complicated compartmental model predicted that, when newly absorbed copper first enters the blood, 74% is removed by the liver and 99% is bound to ceruloplasmin in the plasma. The exchangeable pool of copper was estimated to be 43 +/- 30 mg. Daily endogenous losses were predicted to be 2.4 mg.Conclusions: The results showed that fecal monitoring is the only method that can reliably measure labeled copper absorption, and it is not necessary to administer an intravenous dose of copper to estimate endogenous losses. The compartmental model provides new insights into human copper metabolism.