Papin Jason A, Price Nathan D, Edwards Jeremy S, Palsson B Bernhard Ø
Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
J Theor Biol. 2002 Mar 7;215(1):67-82. doi: 10.1006/jtbi.2001.2499.
Genome-scale metabolic networks can be characterized by a set of systemically independent and unique extreme pathways. These extreme pathways span a convex, high-dimensional space that circumscribes all potential steady-state flux distributions achievable by the defined metabolic network. Genome-scale extreme pathways associated with the production of non-essential amino acids in Haemophilus influenzae were computed. They offer valuable insight into the functioning of its metabolic network. Three key results were obtained. First, there were multiple internal flux maps corresponding to externally indistinguishable states. It was shown that there was an average of 37 internal states per unique exchange flux vector in H. influenzae when the network was used to produce a single amino acid while allowing carbon dioxide and acetate as carbon sinks. With the inclusion of succinate as an additional output, this ratio increased to 52, a 40% increase. Second, an analysis of the carbon fates illustrated that the extreme pathways were non-uniformly distributed across the carbon fate spectrum. In the detailed case study, 45% of the distinct carbon fate values associated with lysine production represented 85% of the extreme pathways. Third, this distribution fell between distinct systemic constraints. For lysine production, the carbon fate values that represented 85% of the pathways described above corresponded to only 2 distinct ratios of 1:1 and 4:1 between carbon dioxide and acetate. The present study analysed single outputs from one organism, and provides a start to genome-scale extreme pathways studies. These emergent system-level characterizations show the significance of metabolic extreme pathway analysis at the genome-scale.
基因组规模的代谢网络可以由一组系统独立且独特的极端途径来表征。这些极端途径跨越一个凸的高维空间，该空间限定了由定义的代谢网络可实现的所有潜在稳态通量分布。计算了与流感嗜血杆菌中非必需氨基酸产生相关的基因组规模极端途径。它们为其代谢网络的功能提供了有价值的见解。获得了三个关键结果。首先，存在多个对应于外部不可区分状态的内部通量图。结果表明，当该网络用于产生单一氨基酸同时允许二氧化碳和乙酸盐作为碳汇时，流感嗜血杆菌中每个独特的交换通量向量平均有37个内部状态。当加入琥珀酸盐作为额外输出时，这个比例增加到52，增加了40%。其次，对碳命运的分析表明，极端途径在碳命运谱上分布不均匀。在详细的案例研究中，与赖氨酸产生相关的45%的不同碳命运值代表了85%的极端途径。第三，这种分布落在不同的系统约束之间。对于赖氨酸产生，代表上述85%途径的碳命运值仅对应于二氧化碳和乙酸盐之间1:1和4:1这2个不同的比例。本研究分析了来自一个生物体的单一输出，并为基因组规模极端途径研究提供了一个开端。这些新出现的系统水平特征显示了基因组规模代谢极端途径分析的重要性。
