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Nathan D Price

Publications and source records attributed to Nathan D Price.

20 records · Page 2Linked to original sources

Determination of redundancy and systems properties of the metabolic network of Helicobacter pylori using genome-scale extreme pathway analysis.

The capabilities of genome-scale metabolic networks can be described through the determination of a set of systemically independent and unique flux maps called extreme pathways. The first study of genome-scale extreme pathways for the simultaneous formation of all nonessential amino acids or ribonucleotides in Helicobacter pylori is presented. Three key results were obtained. First, the extreme pathways for the production of individual amino acids in H. pylori showed far fewer internal states per external state than previously found in Haemophilus influenzae, indicating a more rigid metabolic network. Second, the degree of pathway redundancy in H. pylori was essentially the same for the production of individual amino acids and linked amino acid sets, but was approximately twice that of the production of the ribonucleotides. Third, the metabolic network of H. pylori was unable to achieve extensive conversion of amino acids consumed to the set of either nonessential amino acids or ribonucleotides and thus diverted a large portion of its nitrogen to ammonia production, a potentially important result for pH regulation in its acidic habitat. Genome-scale extreme pathways elucidate emergent system-wide properties. Extreme pathway analysis is emerging as a potentially important method to analyze the link between the metabolic genotype and its phenotypes.

Amino Acids↗

Extreme pathway lengths and reaction participation in genome-scale metabolic networks.

Extreme pathways are a unique and minimal set of vectors that completely characterize the steady-state capabilities of genome-scale metabolic networks. A framework is provided to mathematically characterize extreme pathway length and to study how individual reactions participate in the extreme pathway structure of a network. The length of an extreme pathway is the number of reactions that comprise it. Reaction participation is the percentage of extreme pathways that utilize a given reaction. These properties were computed for the production of individual amino acids and protein production in Helicobacter pylori and individual amino acid production in Haemophilus influenzae. Reaction participation classifies the reactions into groups that are always, sometimes, or never utilized for the production of a target product. The utilized reactions can be further grouped into correlated subsets of reactions, some of which are non-obvious, and which may, in turn, suggest regulatory structure. The length of the extreme pathways did not correlate with product yield or chemical complexity. The distributions of extreme pathway lengths in H. pylori were also very different from those in H. influenzae, showing a distinct systemic difference between the two organisms, despite overall similar metabolic networks. Reaction participation and extreme pathway lengths thus serve to elucidate systemic biological features.

Computational Biology↗