{"id":"bd3a3cfb-45ba-5643-b398-d23ef4a9f661","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-rfc-thdp-shared-pocket","predicate":"binds","statement":"Human SLC19A1 bound thiamine diphosphate in the same pocket as 5-MTHF; thiamine diphosphate inhibited methotrexate uptake with IC50 about 19 micromolar.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"f87227c6-4e8d-51a5-b9ba-3d14af49b05e","mechanism_event_label":"A vitamin B1 cofactor can occupy the folate carrier.","subject":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"object":{"id":"61cc45e4-4f8d-5e18-8473-7aab0dde6d22","slug":"slc19a1","display_name":"Human reduced folate carrier / SLC19A1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f87227c6-4e8d-51a5-b9ba-3d14af49b05e","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:folate-rfc-thdp-shared-pocket-event","event_type":"biochemical_relationship","label":"A vitamin B1 cofactor can occupy the folate carrier.","description":"Human SLC19A1 bound thiamine diphosphate in the same pocket as 5-MTHF; thiamine diphosphate inhibited methotrexate uptake with IC50 about 19 micromolar.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"61cc45e4-4f8d-5e18-8473-7aab0dde6d22","slug":"slc19a1","display_name":"Human reduced folate carrier / SLC19A1","entity_type_key":"protein"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"23f48782-478e-5f62-874a-31273c075fe7","slug":"5-methyltetrahydrofolate","display_name":"5-Methyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"shared-pocket ligand","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1f13ebf9-42c9-516e-b462-0e1b3952c2a2","slug":"methotrexate","display_name":"Methotrexate","entity_type_key":"small_molecule"},"role":"transport probe","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"parent nutrient","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B1-folate: phosphorylated thiamine and folates share RFC recognition; exclusive physiological counter-substrate status remains unproven.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human SLC19A1 structures and HEK293F uptake assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Binding assays and extracellular competition","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Supports shared recognition; does not prove dietary B1 deficiency blocks folate delivery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"folate","display_name":"Folate (vitamin B9)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A vitamin B1 cofactor can occupy the folate carrier.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified transporter and HEK293F cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"9692a54f-20e6-5ee1-8cd3-2a4bf9c422d1","evidence_kind":"source_excerpt","locator":"Lines 167-178","start_line":167,"end_line":178,"excerpt":"### folate-rfc-thdp-shared-pocket\nHuman SLC19A1 bound thiamine diphosphate in the same pocket as 5-MTHF; thiamine diphosphate inhibited methotrexate uptake with IC50 about 19 micromolar.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A vitamin B1 cofactor can occupy the folate carrier.\norganism: Homo sapiens\ntissue_or_cell_type: Purified transporter and HEK293F cells\nexperimental_model: Human SLC19A1 structures and HEK293F uptake assays\nlimitations: Supports shared recognition; does not prove dietary B1 deficiency blocks folate delivery.\nexposure: Binding assays and extracellular competition\ncross_nutrient: B1-folate: phosphorylated thiamine and folates share RFC recognition; exclusive physiological counter-substrate status remains unproven.\n[dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w","model_system":"Human SLC19A1 structures and HEK293F uptake assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f4ce1a62-9582-5f7a-84f5-a23d0e1bfc68","stable_key":"import-ec174d5a-4903-5745-8646-df0e9d4265e8","title":"Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e564d43989ece1006c95cd0748e9af6fe369074599a2eebba0a99ebff864b0dd","revision_id":"76674a33-b2a1-5e41-b71b-44399038ff7c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}