Rhea--a manually curated resource of biochemical reactions

Abstract

Rhea (http://www.ebi.ac.uk/rhea) is a comprehensive resource of expert-curated biochemical reactions. Rhea provides a non-redundant set of chemical transformations for use in a broad spectrum of applications, including metabolic network reconstruction and pathway inference. Rhea includes enzyme-catalyzed reactions (covering the IUBMB Enzyme Nomenclature list), transport reactions and spontaneously occurring reactions. Rhea reactions are described using chemical species from the Chemical Entities of Biological Interest ontology (ChEBI) and are stoichiometrically balanced for mass and charge. They are extensively manually curated with links to source literature and other public resources on metabolism including enzyme and pathway databases. This cross-referencing facilitates the mapping and reconciliation of common reactions and compounds between distinct resources, which is a common first step in the reconstruction of genome scale metabolic networks and models.

Figure 1.

Chemical compound issues. (A) The same chemical compound can be described using different names in textual representations of reactions in the IUBMB classification. (B) A chemical compound may exist in different forms that can interchange spontaneously, such as keto and enol tautomers, and reactions may include each of these forms. To illustrate this, RHEA:22580 describes a reaction involving a keto tautomeric form while RHEA:27873 describes a separate reaction involving an enolic form of the same compound. The keto-enol tautomerization reaction RHEA:31295 allows the two reactions to be linked if necessary.

Figure 2.

The relationships between Rhea and databases of chemical compounds, proteins and enzyme classification. ChEBI provides information on chemical compounds for the creation of chemical reactions in Rhea. The resulting Rhea reactions are used in IntEnz to describe the enzymes catalyzing the reactions. ENZYME is generated from IntEnz data and currently uses the textual representation reactions also used by the IUBMB EC list. Also shown are the cross-references provided by Rhea to other resources. These are generated manually and computationally.

Figure 3.

Sample master reaction and associated directional reactions in Rhea. http://www.ebi.ac.uk/rhea/reaction.xhtml?id=15133 RHEA:15133 is a master reaction. This master reaction is described by its chemicals (labels and identifiers in ChEBI), and has no specific direction. The three associated directional reactions are indicated in the section titled ‘Same participants, different directions’. These are: RHEA:15134 (left-to-right), RHEA:15135 (right-to-left) and RHEA:15136 (bidirectional). The section titled ‘Cross-references’ lists all related resources to which one of the directional reactions has been linked. The actual Rhea reaction can be determined from the directional icon (‘=>’ for RHEA:15134, ‘<=’ for RHEA:15135 and ‘<=>’ for RHEA:15136). The user can retrieve a list of all the reactions a specific compound is involved in by clicking the binocular symbol next to the compound name. Marvin is used for displaying chemical structures, Marvin 5.0.0, 2011 (http://www.chemaxon.com).