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Pathways · Database

MetaCyc

Curated database of experimentally elucidated metabolic pathways, reactions, and enzymes across all domains of life.

What MetaCyc is

MetaCyc is a comprehensive database of metabolic pathways, enzymatic reactions, metabolites, and enzymes curated manually from the primary scientific literature. Every pathway and reaction in the database has been experimentally elucidated in at least one organism. Its scope covers both primary and secondary metabolism across all biological domains.

Supported by funding from the National Institute of General Medical Sciences (NIGMS), MetaCyc acts as a non-redundant reference encyclopaedia of metabolism. It compiles rich biochemical descriptions, reaction thermodynamics, and literature citations to provide biochemists, computational biologists, and metabolic engineers with verified catalytic mechanisms.

Beyond functioning as an informational reference, MetaCyc serves as a foundational dataset for computationally predicting the metabolic networks of organisms with sequenced genomes, such as those catalogued in the BioCyc database collection. It also provides reference chemical and pathway structures to support metabolomics research and bioengineering.

How it is organised

MetaCyc is maintained through expert manual curation from scientific publications, drawing evidence from more than 58,000 papers. Curation staff record detailed reaction steps, catalytic enzymes, and corresponding genes. Reactions are stoichiometrically balanced and annotated with Enzyme Commission (EC) numbers, preferred reaction direction, calculated Gibbs free energy values, and predicted atom mappings tracing reactant atoms to product atoms.

Data records are organised into an interconnected relational framework where metabolites, enzymes, and pathways link directly to each other. Metabolite entries supply chemical structures, predicted standard energies of formation, and cross-references to external resources including ChEBI, KEGG, and UniProt. Enzyme entries include subunit structures, essential cofactors, regulatory activators and inhibitors, substrate specificities, and kinetic parameters when documented.

Key facts

Curated pathways
3,284 (also cited as 3.7k)
Curated reactions
20,199 (also cited as 21.4k)
Curated metabolites
20,642
Biological scope
All domains of life
Curation basis
Manual curation of experimental evidence from over 58,000 publications
Search identifiers
Compound names, EC numbers, InChI-keys, internal IDs, locus IDs, organism taxa, and external IDs (UniProt, KEGG, ChEBI)
Primary funding
NIH National Institute of General Medical Sciences (grant GM080746)

What you can use it for

Genome-scale metabolic reconstruction
Computational biologists use MetaCyc as a curated reference library to predict metabolic pathways and reaction networks from newly sequenced and annotated organism genomes.
Metabolic engineering and pathway design
Engineers query enzyme specificities, kinetic constants, cofactors, and reaction routes to design synthetic pathways and select catalytic components for bioengineering.
Metabolomics data interpretation
Researchers match identified metabolite profiles against MetaCyc structures and pathway maps to identify affected biological processes and contextualise experimental findings.
Enzymology and pathway literature lookup
Biochemists review mini-reviews, kinetic parameters, inhibitors, activators, and balanced thermodynamic properties for specific enzymes and multi-step pathways.

Strengths and limits

Good at

  • All pathways and reactions are manually curated from primary literature and experimentally validated in at least one organism.
  • Reaction entries are chemically balanced and supplied with predicted atom mappings and calculated Gibbs free energy values.
  • Enzyme records provide in-depth biochemical context, including subunit compositions, cofactors, regulators, and kinetic constants when available.
  • The repository covers both primary and secondary metabolism across all domains of life.

Watch out for

  • Cross-links to external identifiers such as UniProt, KEGG, and ChEBI are incomplete, meaning external ID searches can fail even if the entity exists in the database.
  • Detailed kinetic parameters are not available for all enzymes and depend strictly on published literature values.

Questions

Can I search MetaCyc without writing code?

MetaCyc is catalogued here but not yet queried live, so the agent can point you to it but cannot search it for you yet.

Can I reuse data from MetaCyc?

MetaCyc publishes its own terms of use; read them on https://metacyc.org before reusing its records.

Are MetaCyc pathways predicted by computational models?

No. MetaCyc only records pathways and reactions that have been experimentally elucidated in at least one organism, although MetaCyc is itself used as a reference to computationally predict pathways in other organisms.

What information is included on reaction pages?

Reaction entries feature a visual display of component chemical structures, stoichiometric balance, reaction direction, EC numbers, computed Gibbs free energy, and predicted atom mappings between reactants and products.

What query parameters are supported when searching MetaCyc?

Searches accept compound, gene, protein, or pathway names and substrings, full or partial EC numbers, InChI-keys, organism and taxon names, internal object identifiers, and external IDs from databases such as UniProt, KEGG, and ChEBI.

Does MetaCyc cover secondary metabolism?

Yes. MetaCyc contains pathways and reactions covering both primary and secondary metabolism.

How to cite it

Caspi et al 2020, "The MetaCyc database of metabolic pathways and enzymes - a 2019 update", Nucleic Acids Research 48(D1):D445-D453

Written from MetaCyc's own website and reference material. Statements citing a figure that does not appear there are removed before publication. Licence and running details come from our registry.