Calculation of the synthesizing capacity of metabolic networks when provided with specified external resources [read more...]
For a given network and predefined external resources (seed metabolites), the algorithm calculates those chemical compounds which the network is in principle able to produce. This set of products is called the scope of the seed and characterizes the biosynthetic capacity of the network.
Starting with given seed metabolites the algorithm selects from a database in an iterative manner those reactions, whose substrates are either part of the set of seed compounds or are products of reactions which were already selected in an earlier iteration step. This network expansion process ends when no further reactions fulfilling this condition can be found. All metabolites which can be produced by the resulting set of reactions form the scope of the seed compounds. Scopes describe therefore the synthesizing capacity of the corresponding seed compounds in a specified metabolic network.
Enzyme catalyzed reactions can in principle proceed in forward as well as in backward direction. However, under physiological conditions the metabolite concentrations may be such that one direction is thermodynamically unfeasible. The expansion algorithm can consider both, irreversible and reversible reactions, where reversible reactions are utilized if either all their substrates or all their products were present in the last iteration step.
Variants of the expansion algorithm have been implemented, in which reactions utilizing cofactors can also be included even if the cofactor has not been synthesized from the seed compounds. The algorithm ensures that in such a case the cofactor can only be used in its function as cofactor, for example as phosphate donor in the case of ATP, but not as a substrate for the synthesis of other metabolites.