Extreme pathway analysis of human red blood cell metabolism
Extreme pathway analysis of human red blood cell metabolism
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DOI：
10.1016/s0006-3495(02)75210-7
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Palsson, BO
中科院分区：
文献类型：
--
作者：
Wiback, SJ;Palsson, BO
高通量技术的发展和由此产生的大规模数据集需要一种系统的方法来分析代谢网络。解决复杂代谢功能问题的一种方法是通过极端途径的计算和解释。极端路径是一组数学定义的生成向量，用于描述整个代谢网络中通量分布的锥形稳态解空间。在此，在生化和生理学的背景下，计算和解释了表征良好的人类红细胞代谢网络的极端途径。这些极端途径根据辅助因子和副产物的产生以及碳输入（包括1）将葡萄糖转化为丙酮酸；2)丙酮酸与乳酸交换；3)产生与血红蛋白结合的2,3-二磷酸甘油酸；4)将肌苷转化为丙酮酸；5)诱导总腺苷池的改变；6)耗散ATP。此外，红细胞代谢的完整动力学模型的结果仅基于对极端途径结构的解释来预测。因此，红细胞的极端途径给出了红细胞代谢的简明表示和解释其代谢生理学的一种方法。
The development of high-throughput technologies and the resulting large-scale data sets have necessitated a systems approach to the analysis of metabolic networks. One way to approach the issue of complex metabolic function is through the calculation and interpretation of extreme pathways. Extreme pathways are a mathematically defined set of generating vectors that describe the conical steady-state solution space for flux distributions through an entire metabolic network. Herein, the extreme pathways of the well-characterized human red blood cell metabolic network were calculated and interpreted in a biochemical and physiological context. These extreme pathways were divided into groups based on such criteria as their cofactor and by-product production, and carbon inputs including those that 1) convert glucose to pyruvate; 2) interchange pyruvate and lactate; 3) produce 2,3-diphosphoglycerate that binds to hemoglobin; 4) convert inosine to pyruvate; 5) induce a change in the total adenosine pool; and 6) dissipate ATP. Additionally, results from a full kinetic model of red blood cell metabolism were predicted based solely on an interpretation of the extreme pathway structure. The extreme pathways for the red blood cell thus give a concise representation of red blood cell metabolism and a way to interpret its metabolic physiology.