Reaction curation



Rhea is an expert-curated knowledgebase of chemical and transport reactions of biological interest. Enzyme-catalyzed and spontaneously occurring reactions are curated from peer-reviewed literature and represented in a computationally tractable manner using the chemical dictionary ChEBI (Chemical Entities of Biological Interest) to describe reaction participants.


Rhea collaborates with and complements the work of three related resources:

ResourceData type
ChEBIreaction participant
UniProtKBenzyme sequence and functional information
ENZYMEenzyme classification (see details)

Rhea curators describe reactions using ChEBI entities. They submit new entities and updates (synonyms, citations, links, relationships, structure) to ChEBI that are then reviewed by CHEBI curators. UniProt provides sequence and functional information for proteins and uses Rhea to describe enzyme-catalyzed and transporter reactions. ENZYME curators create enzyme classes (EC numbers) according to the NC-IUBMB recommendations and link them to Rhea reactions. Both UniProt and ENZYME curators request new reactions from Rhea.


These collaborations and user requests drive our curation priorities and the scope of Rhea, which includes all enzyme-catalyzed reactions covered by the NC-IUBMB enzyme classification, but also many more that are described in UniProtKB and other resources, as well as spontaneously occurring reactions.


Curation steps

Identify relevant scientific publications

Rhea curators scan the scientific literature to identify publications on novel reactions. They select the most relevant publication(s) to curate a new Rhea reaction. They cite the publications by their PubMed identifiers. The same publication may provide evidence for multiple reactions.

Rhea also collaborates with PubTator Central (NIH) to identify publications that describe reactions that are missing in Rhea.

Encode the reaction participants with ChEBI

Rhea curators search the ChEBI ontology for compounds that match the description of the reaction participants that they found in the literature. If they cannot find a suitable compound, they submit a draft for a new compound to ChEBI, which is then reviewed by CHEBI curators. For reactions that involve macromolecules or polymers, Rhea curators create compound records in Rhea to encode these molecules (see reaction participants).


Ensure that the reaction is chemically balanced at pH 7.3 and non redundant

Rhea curators use software to check that:

  1. all reaction participants correspond to the major microspecies at pH 7.3
  2. mass and charge are balanced, i.e. the sum of the formulas and charges of the two reaction sides are identical
  3. the reaction is non redundant


Classify the reaction

If possible, Rhea curators classify the reaction (see details).

Rhea curators compare the reaction to those in other metabolic resources like MetaCyc, EcoCyc and KEGG. If they find an equivalent reaction, they add a link to its identifier. Note that sometimes the linked reaction is not 100% identical, it may differ by a stereo center or the protonation state due to a different curation policy.

Rhea also automatically imports links to Rhea reactions from other resources that curate (or predict) them:

  • UniProt curators and the UniProt automatic annotation pipeline link protein sequences to Rhea reactions.
  • ENZYME curators link EC numbers to Rhea reactions.
  • Gene Ontology curators link GO 'Molecular Functions' concepts to Rhea reactions.

Mappings of Rhea reactions to records in other resources are available on our Download page.

Quality assessment

All Rhea reactions are reviewed by two curators.

Give us feedback!

If you do not find the reaction that you need, do not hesitate to request it via our Feedback form. Please include the PubMed identifier of the article that describes the experimental evidence for the reaction.