title: Analysis of metabolic networks using a pathway distance metric through linear programming.
abstract: The solution of the shortest path problem in biochemical systems constitutes an important step for studies of their evolution. In this paper, a linear programming (LP) algorithm for calculating minimal pathway distances in metabolic networks is studied. Minimal pathway distances are identified as the smallest number of metabolic steps separating two enzymes in metabolic pathways. The algorithm deals effectively with circularity and reaction directionality. The applicability of the algorithm is illustrated by calculating the minimal pathway distances for Escherichia coli small molecule metabolism enzymes, and then considering their correlations with genome distance (distance separating two genes on a chromosome) and enzyme function (as characterised by enzyme commission number). The results illustrate the effectiveness of the LP model. In addition, the data confirm that propinquity of genes on the genome implies similarity in function (as determined by co-involvement in the same region of the metabolic network), but suggest that no correlation exists between pathway distance and enzyme function. These findings offer insight into the probable mechanism of pathway evolution.
authors.affiliation: Department of Chemical Engineering, Centre for Process Systems Engineering, UCL, London, WC1E 7JE, UK.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Simeonidis
authors.forename: Stuart C G
authors.initials: SC
authors.lastname: Rison
authors.forename: Janet M
authors.initials: JM
authors.lastname: Thornton
authors.forename: I David L
authors.initials: ID
authors.lastname: Bogle
authors.forename: Lazaros G
authors.initials: LG
authors.lastname: Papageorgiou
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D008660:Metabolism / Q000502:physiology*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism*; D009716:Numerical Analysis, Computer-Assisted; D011382:Programming, Linear
chemical_list: D009097:Multienzyme Complexes