Tracing metabolic pathways from enzyme data.

The IUBMB Enzyme List is widely used by other databases as a source for avoiding ambiguity in the recognition of enzymes as catalytic entities. However, it was never designed for activities such as pathway tracing, which have become increasingly important in systems biology. This is because it often relies on generic or representative reactions to show the reactions catalysed by enzymes of wide specificity. It is necessary to go to databases such as BRENDA to find further, more detailed, information on what is known about the range of substrates for any particular enzyme. In order to provide a framework for tracing pathways involving any specific enzyme or metabolite, we have created a Reactions Database from the material in the Enzyme List. This allows reactions to be searched by substrate/product and pathways to be traced from any selected starting/seed substrate. An extensive synonym glossary allows searches by many of the alternative names, including accepted abbreviations, by which a chemical compound may be known. This database was necessary for the development of the application Reaction Explorer (http://www.reaction-explorer.org), which was written in REALbasic to search the Reactions Database and draw metabolic pathways from reactions selected by the user. Having input the name of the starting compound (the "seed"), the user is presented with a list of all reactions containing that compound and then selects the product of interest as the next point on the ensuing graph. The pathway diagram is then generated as the process iterates. A contextual menu is provided, which allows the user to (i) remove a compound from the graph, along with all associated links; (ii) search the reactions database again for additional reactions involving the compound and (iii) search for the compound within the Enzyme List.

ExplorEnz: the primary source of the IUBMB enzyme list.

ExplorEnz is the MySQL database that is used for the curation and dissemination of the International Union of Biochemistry and Molecular Biology (IUBMB) Enzyme Nomenclature. A simple web-based query interface is provided, along with an advanced search engine for more complex Boolean queries. The WWW front-end is accessible at http://www.enzyme-database.org, from where downloads of the database as SQL and XML are also available. An associated form-based curatorial application has been developed to facilitate the curation of enzyme data as well as the internal and public review processes that occur before an enzyme entry is made official. Suggestions for new enzyme entries, or modifications to existing ones, can be made using the forms provided at http://www.enzyme-database.org/forms.php.

Eliciting possible reaction equations and metabolic pathways involving orphan metabolites.

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.

Functional group and substructure searching as a tool in metabolomics.

BACKGROUND: A direct link between the names and structures of compounds and the functional groups contained within them is important, not only because biochemists frequently rely on literature that uses a free-text format to describe functional groups, but also because metabolic models depend upon the connections between enzymes and substrates being known and appropriately stored in databases. METHODOLOGY: We have developed a database named "Biochemical Substructure Search Catalogue" (BiSSCat), which contains 489 functional groups, >200,000 compounds and >1,000,000 different computationally constructed substructures, to allow identification of chemical compounds of biological interest. CONCLUSIONS: This database and its associated web-based search program (http://bisscat.org/) can be used to find compounds containing selected combinations of substructures and functional groups. It can be used to determine possible additional substrates for known enzymes and for putative enzymes found in genome projects. Its applications to enzyme inhibitor design are also discussed.

ExplorEnz: a MySQL database of the IUBMB enzyme nomenclature.

BACKGROUND: We describe the database ExplorEnz, which is the primary repository for EC numbers and enzyme data that are being curated on behalf of the IUBMB. The enzyme nomenclature is incorporated into many other resources, including the ExPASy-ENZYME, BRENDA and KEGG bioinformatics databases. DESCRIPTION: The data, which are stored in a MySQL database, preserve the formatting of chemical and enzyme names. A simple, easy to use, web-based query interface is provided, along with an advanced search engine for more complex queries. The database is publicly available at http://www.enzyme-database.org. The data are available for download as SQL and XML files via FTP. CONCLUSION: ExplorEnz has powerful and flexible search capabilities and provides the scientific community with the most up-to-date version of the IUBMB Enzyme List.

Monoamine oxidases: certainties and uncertainties.

A great deal has been learned about the behaviour of monoamine oxidase in the 75 years since it was first discovered, but there is still a great deal left to understand. This review concentrates on the dynamic aspects of our knowledge of the interactions of MAO with substrates and inhibitors and how it may collaborate with other enzymes, with particular emphasis on aspects that remain to be clarified.

IntEnz, the integrated relational enzyme database.

IntEnz is the name for the Integrated relational Enzyme database and is the official version of the Enzyme Nomenclature. The Enzyme Nomenclature comprises recommendations of the Nomenclature Committee of the International Union of Bio chemistry and Molecular Biology (NC-IUBMB) on the nomenclature and classification of enzyme-catalysed reactions. IntEnz is supported by NC-IUBMB and contains enzyme data curated and approved by this committee. The database IntEnz is available at http://www.ebi.ac.uk/intenz.