tetrahydrofolate biosynthesis

gomodel:YeastPathways_PWY-6614

tetrahydrofolate biosynthesis in Saccharomyces cerevisiae S288C converts 4-aminobenzoate and (7,8-dihydropterin-6-yl)methyl diphosphate to tetrahydrofolate through FOL1-catalyzed dihydropteroate synthase activity, FOL3-catalyzed dihydrofolate synthase activity, and DFR1-catalyzed dihydrofolate reductase activity.

Pathway type

folate biosynthesis

Organism scope

Saccharomyces cerevisiae S288C NCBITaxon:559292

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Pathway network

24 nodes · 29 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Reaction / activity
Chemical / cofactor
Protein / complex
Cell / process context
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Saccharomyces cerevisiae S288C `NCBITaxon:559292`	taxon
dihydrofolate(2-) `CHEBI:57451`	small molecule
tetrahydrofolate biosynthetic process `GO:0046654`	biological process
ADP(3-) `CHEBI:456216`	small molecule
cytosol `GO:0005829`	cellular component
NADPH(4-) `CHEBI:57783`	small molecule
7,8-dihydropteroate `CHEBI:17839`	small molecule
tetrahydrofolate `CHEBI:67016`	small molecule
4-aminobenzoate `CHEBI:17836`	small molecule
ATP(4-) `CHEBI:30616`	small molecule
diphosphoric acid `CHEBI:29888`	small molecule
(7,8-dihydropterin-6-yl)methyl diphosphate `CHEBI:73083`	small molecule
L-glutamate(1-) `CHEBI:29985`	small molecule
hydron `CHEBI:15378`	small molecule
FOL1 Scer `SGD:S000005200`	protein
FOL3 Scer `SGD:S000004719`	protein
DFR1 Scer `SGD:S000005762`	protein
NADP(3-) `CHEBI:58349`	small molecule
hydrogenphosphate `CHEBI:43474`	small molecule
mitochondrial membrane `GO:0031966`	cellular component
cytoplasm `GO:0005737`	cellular component
magnesium(2+) `CHEBI:18420`	cofactor
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	molecular activity
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	molecular activity
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	molecular activity

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_output	dihydrofolate(2-) `CHEBI:57451`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002234 gomodel:CHEBI_57451_DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/0; endpoint types: /individuals/15/type; /individuals/10/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	part_of	tetrahydrofolate biosynthetic process `GO:0046654`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN BFO:0000050 gomodel:YeastPathways_PWY-6614/YeastPathways_PWY-6614. Source location `./YeastPathways_PWY-6614.json#/facts/1; endpoint types: /individuals/14/type; /individuals/44/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_output	ADP(3-) `CHEBI:456216`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002234 gomodel:CHEBI_456216_DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/2; endpoint types: /individuals/15/type; /individuals/8/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	has_input	dihydrofolate(2-) `CHEBI:57451`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN RO:0002233 gomodel:CHEBI_57451_DIHYDROFOLATEREDUCT-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/3; endpoint types: /individuals/14/type; /individuals/9/type`
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	provides_input_for	dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN RO:0002413 gomodel:DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/5; endpoint types: /individuals/16/type; /individuals/15/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	has_input	NADPH(4-) `CHEBI:57783`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN RO:0002233 gomodel:CHEBI_57783_DIHYDROFOLATEREDUCT-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/6; endpoint types: /individuals/14/type; /individuals/11/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	occurs_in	cytosol `GO:0005829`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN BFO:0000066 gomodel:reaction_DIHYDROFOLATESYNTH-RXN_location_lociGO_0005829. Source location `./YeastPathways_PWY-6614.json#/facts/7; endpoint types: /individuals/15/type; /individuals/42/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_input	7,8-dihydropteroate `CHEBI:17839`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002233 gomodel:CHEBI_17839_H2PTEROATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/8; endpoint types: /individuals/15/type; /individuals/3/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	has_output	tetrahydrofolate `CHEBI:67016`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN RO:0002234 gomodel:YeastPathways_PWY-6614/6690711d00000586. Source location `./YeastPathways_PWY-6614.json#/facts/9; endpoint types: /individuals/14/type; /individuals/46/type`
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	has_input	4-aminobenzoate `CHEBI:17836`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN RO:0002233 gomodel:CHEBI_17836_H2PTEROATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/10; endpoint types: /individuals/16/type; /individuals/2/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_input	ATP(4-) `CHEBI:30616`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002233 gomodel:CHEBI_30616_DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/11; endpoint types: /individuals/15/type; /individuals/6/type`
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	has_output	diphosphoric acid `CHEBI:29888`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN RO:0002234 gomodel:CHEBI_29888_H2PTEROATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/12; endpoint types: /individuals/16/type; /individuals/4/type`
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	has_input	(7,8-dihydropterin-6-yl)methyl diphosphate `CHEBI:73083`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN RO:0002233 gomodel:CHEBI_73083_H2PTEROATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/13; endpoint types: /individuals/16/type; /individuals/13/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	occurs_in	cytosol `GO:0005829`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN BFO:0000066 gomodel:reaction_DIHYDROFOLATEREDUCT-RXN_location_lociGO_0005829. Source location `./YeastPathways_PWY-6614.json#/facts/14; endpoint types: /individuals/14/type; /individuals/41/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_input	L-glutamate(1-) `CHEBI:29985`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002233 gomodel:CHEBI_29985_DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/15; endpoint types: /individuals/15/type; /individuals/5/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_output	hydron `CHEBI:15378`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002234 gomodel:CHEBI_15378_DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/16; endpoint types: /individuals/15/type; /individuals/1/type`
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	part_of	tetrahydrofolate biosynthetic process `GO:0046654`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN BFO:0000050 gomodel:YeastPathways_PWY-6614/YeastPathways_PWY-6614. Source location `./YeastPathways_PWY-6614.json#/facts/17; endpoint types: /individuals/16/type; /individuals/44/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	part_of	tetrahydrofolate biosynthetic process `GO:0046654`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN BFO:0000050 gomodel:YeastPathways_PWY-6614/YeastPathways_PWY-6614. Source location `./YeastPathways_PWY-6614.json#/facts/18; endpoint types: /individuals/15/type; /individuals/44/type`
FOL1 Scer `SGD:S000005200`	enables	dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN RO:0002333 gomodel:YNL256W-MONOMER_H2PTEROATESYNTH-RXN_controller. Source location `./YeastPathways_PWY-6614.json#/facts/19; endpoint types: /individuals/16/type; /individuals/18/type`
FOL3 Scer `SGD:S000004719`	enables	dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002333 gomodel:YMR113W-MONOMER_DIHYDROFOLATESYNTH-RXN_controller. Source location `./YeastPathways_PWY-6614.json#/facts/20; endpoint types: /individuals/15/type; /individuals/17/type`
DFR1 Scer `SGD:S000005762`	enables	dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN RO:0002333 gomodel:YOR236W-MONOMER_DIHYDROFOLATEREDUCT-RXN_controller. Source location `./YeastPathways_PWY-6614.json#/facts/21; endpoint types: /individuals/14/type; /individuals/19/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	causally_upstream_of	dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002411 gomodel:DIHYDROFOLATEREDUCT-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/22; endpoint types: /individuals/15/type; /individuals/14/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	has_input	hydron `CHEBI:15378`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN RO:0002233 gomodel:CHEBI_15378_DIHYDROFOLATEREDUCT-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/23; endpoint types: /individuals/14/type; /individuals/0/type`
dihydrofolate reductase activity `gomodel:DIHYDROFOLATEREDUCT-RXN`	has_output	NADP(3-) `CHEBI:58349`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATEREDUCT-RXN RO:0002234 gomodel:CHEBI_58349_DIHYDROFOLATEREDUCT-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/24; endpoint types: /individuals/14/type; /individuals/12/type`
dihydrofolate synthase activity `gomodel:DIHYDROFOLATESYNTH-RXN`	has_output	hydrogenphosphate `CHEBI:43474`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:DIHYDROFOLATESYNTH-RXN RO:0002234 gomodel:CHEBI_43474_DIHYDROFOLATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/25; endpoint types: /individuals/15/type; /individuals/7/type`
dihydropteroate synthase activity `gomodel:H2PTEROATESYNTH-RXN`	has_output	7,8-dihydropteroate `CHEBI:17839`	gomodel:YeastPathways_PWY-6614 Source assertion: The model asserts gomodel:H2PTEROATESYNTH-RXN RO:0002234 gomodel:CHEBI_17839_H2PTEROATESYNTH-RXN. Source location `./YeastPathways_PWY-6614.json#/facts/26; endpoint types: /individuals/16/type; /individuals/3/type`
FOL1 Scer `SGD:S000005200`	located_in Physical protein location from reviewed UniProt. ECO:0000269 (PubMed:14576278); ECO:0000269 (PubMed:15169867)	mitochondrial membrane `GO:0031966`	UniProtKB:P53848 Source assertion: UniProtKB:P53848 annotates location Mitochondrion membrane (SL-0171). Source location `https://rest.uniprot.org/uniprotkb/stream?query=taxonomy_id%3A559292+AND+reviewed%3Atrue&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_subcellular_location%2Ccc_function%2Ccc_caution%2Corganism_id#/results/2262/comments/1/subcellularLocations/0; sha256=95f72dcc644358c480e0e59f996cf88533558b5fa4256460a030e0a1eaf9678d` UniProtKB:P53848 Source assertion: UniProtKB:P53848 has the exact SGD cross-reference SGD:S000005200. Source location `https://rest.uniprot.org/uniprotkb/stream?query=taxonomy_id%3A559292+AND+reviewed%3Atrue&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_subcellular_location%2Ccc_function%2Ccc_caution%2Corganism_id#/results/2262/uniProtKBCrossReferences/0; sha256=95f72dcc644358c480e0e59f996cf88533558b5fa4256460a030e0a1eaf9678d`
FOL3 Scer `SGD:S000004719`	located_in Physical protein location from reviewed UniProt. ECO:0000269 (PubMed:14562095)	cytoplasm `GO:0005737`	UniProtKB:Q12676 Source assertion: UniProtKB:Q12676 annotates location Cytoplasm (SL-0086). Source location `https://rest.uniprot.org/uniprotkb/stream?query=taxonomy_id%3A559292+AND+reviewed%3Atrue&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_subcellular_location%2Ccc_function%2Ccc_caution%2Corganism_id#/results/5113/comments/1/subcellularLocations/0; sha256=95f72dcc644358c480e0e59f996cf88533558b5fa4256460a030e0a1eaf9678d` UniProtKB:Q12676 Source assertion: UniProtKB:Q12676 has the exact SGD cross-reference SGD:S000004719. Source location `https://rest.uniprot.org/uniprotkb/stream?query=taxonomy_id%3A559292+AND+reviewed%3Atrue&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_subcellular_location%2Ccc_function%2Ccc_caution%2Corganism_id#/results/5113/uniProtKBCrossReferences/0; sha256=95f72dcc644358c480e0e59f996cf88533558b5fa4256460a030e0a1eaf9678d`
FOL1 Scer `SGD:S000005200`	has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 (UniProtKB:P0AC13)	magnesium(2+) `CHEBI:18420`	UniProtKB:P53848 Source assertion: UniProtKB:P53848 annotates CHEBI:18420 as a cofactor of this protein. Source location `https://rest.uniprot.org/uniprotkb/stream?query=taxonomy_id%3A559292+AND+reviewed%3Atrue&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_cofactor%2Corganism_id%2Ccc_caution [sha256:1378282d22c5518215707964664b55946f468ba74a227a6ea1bbf27db69ddbc4] #/results/2262/comments/0/cofactors/0` UniProtKB:P53848 Source assertion: UniProtKB:P53848 has the exact SGD cross-reference SGD:S000005200. Source location `https://rest.uniprot.org/uniprotkb/stream?query=taxonomy_id%3A559292+AND+reviewed%3Atrue&format=json&fields=accession%2Cprotein_name%2Cxref_sgd%2Ccc_cofactor%2Corganism_id%2Ccc_caution [sha256:1378282d22c5518215707964664b55946f468ba74a227a6ea1bbf27db69ddbc4] #/results/2262/uniProtKBCrossReferences/0`

References

gomodel:YeastPathways_PWY-6614 GO-CAM tetrahydrofolate biosynthesis model YeastPathways_PWY-6614 (source version: Pinned Noctua JSON archive; model date 2026-08-05; member ./YeastPathways_PWY-6614.json)
UniProtKB:P53848 Reviewed UniProtKB P53848 location annotations (source version: UniProt release 2026_03)
UniProtKB:Q12676 Reviewed UniProtKB Q12676 location annotations (source version: UniProt release 2026_03)

Curation history

2026-10-05T06:05:08Z Codex; review-causal-graph; Reviewed every native GO-CAM fact; preserved precise input/output, causal, location, membership and complex-part relations with traceable structured source evidence. Kept distinct generic physical instances and recorded source-scope exclusions in the cohort review ledger.
2026-10-05T06:43:56Z Codex
- EDIT — Audit causal activity compartments and preserve scoped protein location evidence
  Reviewed all 3 activity location assignments and 3 mapped physical proteins against reviewed S288C UniProt release2026_03 location/function/caution batch SHA256 95f72dcc644358c480e0e59f996cf88533558b5fa4256460a030e0a1eaf9678d. Added 2 independently supported location edges and quarantined 1 generic cytosol source assertions. Mapped physical protein locations via exact SGD cross-references; retained source ECO grades, molecular form and conditional notes. Physical protein location alone never generates activity location. Explicitly inspected functional assertions support bounded activity projections. Every original activity location and exclusion is recorded in reports/causal_graph_review/gocam-location-review.json. No independent location annotation is treated as an evidence gap, not a negative result. Cytoplasm is not narrowed to cytosol. Microsome fractions are not projected as in-vivo organelles. Semantic validation passed all85 records;4 independent source-role acceptance tests passed.
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