Biochemically detailed stoichiometric matrices have now been reconstructed for various bacteria, yeast, and for the human cardiac mitochondrion based on genomic and proteomic data. These networks have been manually curated based on legacy data and elementally and charge balanced. Comparative analysis of these well curated networks is now possible. Pairs of metabolites often appear together in several network reactions, linking them topologically. This co-occurrence of pairs of metabolites in metabolic reactions is termed herein metabolite coupling. These metabolite pairs can be directly computed from the stoichiometric matrix, S. Metabolite coupling is derived from the matrix xc5x9dxc5x9dT, whose off-diagonal elements indicate the number of reactions in which any two metabolites participate together, where xc5x9d is the binary form of S.