{"id":"5f0c5ba5-90d0-5ddb-86df-155804812488","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:shmt1-reverse-flux-replete","predicate":"supports-synthesis-of","statement":"In nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"c9fffbe1-6bd9-5365-b89e-a2355f16cff1","mechanism_event_label":"SHMT1 can consume one-carbon units instead of producing them.","subject":{"id":"67b21ade-d4c1-574a-a78f-b980d076ad9c","slug":"shmt1","display_name":"SHMT1","entity_type_key":"protein"},"object":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"c9fffbe1-6bd9-5365-b89e-a2355f16cff1","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:shmt1-reverse-flux-replete-event","event_type":"biochemical_relationship","label":"SHMT1 can consume one-carbon units instead of producing them.","description":"In nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"2b507258-430c-51fe-9fd2-e510c2c197a9","slug":"glycine","display_name":"Glycine","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0413b195-325e-5757-a72b-f445d65c17bc","slug":"5-10-methylenetetrahydrofolate","display_name":"5,10-Methylenetetrahydrofolate","entity_type_key":"small_molecule"},"role":"one-carbon donor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"existing B6 cofactor relationship","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"67b21ade-d4c1-574a-a78f-b980d076ad9c","slug":"shmt1","display_name":"SHMT1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Links existing B6-dependent SHMT chemistry to folate flux direction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Stable-isotope tracing","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Assay conditions described in the linked primary study.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not a universal direction across tissues or nutrition states.","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":"SHMT1 can consume one-carbon units instead of producing them.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293T and HCT116 cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ad0c1a64-91d6-5b37-9e1e-ae3ad72c0805","evidence_kind":"source_excerpt","locator":"Lines 923-934","start_line":923,"end_line":934,"excerpt":"### shmt1-reverse-flux-replete\nIn nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: SHMT1 can consume one-carbon units instead of producing them.\norganism: Homo sapiens\ntissue_or_cell_type: HEK293T and HCT116 cells\nexperimental_model: Stable-isotope tracing\nlimitations: Not a universal direction across tissues or nutrition states.\nexposure: Assay conditions described in the linked primary study.\ncross_nutrient: Links existing B6-dependent SHMT chemistry to folate flux direction.\n[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016","model_system":"Stable-isotope tracing","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016","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}