The development of metabolomics has resulted in the discovery of an increasing number of orphan metabolites, which are defined as compounds that are known to be present in living organisms but whose synthetic/degradation pathways are unknown. In this paper, we describe a procedure for identifying possible products and/or precursors of such orphan metabolites and for suggesting complete reaction equations and the corresponding EC (Enzyme Commission) number simultaneously. Chemical structure comparison is performed for a pair of compounds consisting of a reported substrate and its corresponding product and also for pairs of randomly selected compounds. Possible combinations of compounds registered in the KEGG database were used for generating putative enzyme reaction equations, which resulted in 77% of the reported equations being generated, as most of the remainder represent classes of compounds, rather than specific compounds, or contain Markush structures. The quality was checked using chemical structure comparison and the random-tree method, which gave 98% accuracy in suggesting EC subsubclasses for reported equations in cross-validation tests. The equations generated in this study can be seen using the Web-based program GREP (Generator of Reaction Equations & Pathways; http://bisscat.org/GREP/ ). The usefulness of our method for constructing possible metabolic pathways was demonstrated by mapping the generated equations for several groups of compounds, such as the betalain alkaloids. The possible development of our method so that alternative substrates for reported enzymes can be found and for annotating enzyme functions in genomic research is also discussed.