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通过18O标签和模型减少揭示了因诺醇酸盐代谢的线性途径

Jacques Hermes^1,2,3, Geun-Don Kim⁴, Guizhen Liu^3,5

¹Institute of Physics, University of Freiburg, Freiburg, Germany.

PLoS computational biology

|November 10, 2025

概括

细胞内无机酸盐稳态依赖于内醇酸盐 (IPPs). 这项研究揭示了酵母和人体细胞中1,5-InsP8合成的线性代谢途径,挑战了以前的模型.

科学领域:

生物化学生物化学
细胞生物学细胞生物学
系统生物学系统生物学

背景情况:

细胞内无机酸盐平衡对于真核生物代谢至关重要.
伊诺西铁酸盐 (IPP) 信号通路通过使用IPP作为信使来调节酸盐水平.
了解IPP代谢途径对于细胞功能至关重要.

研究的目的:

为了研究伊诺西铁酸盐 (IPPs) 的代谢途径,特别是1,5-InsP8的合成和周转.
为了确定1,5-InsP8是否可以通过酵母和人体细胞的不同途径合成.
应用模型减少技术,以获得对IPP途径的生物学见解.

主要方法:

使用18O水进行脉冲标记实验.
普通微分方程 (ODE) 建模.
通过概率分析方法进行模型缩小.
在酵母淘汰菌株 (vip1Δ和kcs1Δ) 中进行实验验证.

主要成果:

在酵母 (PhoΔSPX) 和人类 (HCT116) 细胞中确定了1,5-InsP8合成的线性反应序列.
在酵母中,1,5-InsP8生产主要通过5-InsP7酸化发生;1-InsP7通路不必.
在HCT116细胞中,1-InsP7是1,5-InsP8合成的主要驱动因素,有条件依赖的变化.

结论:

模型减少有效地提高了对代谢途径的理解.
预测建模与实验验证相结合,提供了强大的生物学见解.
这项研究为研究真核生物中的线性IPP通路提供了一个框架.

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