{"id":"ac857c06-f52a-566d-b680-c24609e91683","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:aldh1l1-aicar-accumulation","predicate":"increases","statement":"Ectopic ALDH1L1 expression in HuH-7 cells increased ZMP/AICAR ribotide, consistent with reduced formyl-donor availability for ATIC.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"6109c7d6-21e2-5aab-8369-ac56537810dc","mechanism_event_label":"Disposing of folate-bound carbon can slow a purine-building step.","subject":{"id":"546aed58-bcd0-5ed1-8b43-c196155dcbac","slug":"aldh1l1","display_name":"Human ALDH1L1","entity_type_key":"protein"},"object":{"id":"4af06f63-38d1-5e5a-be55-69db44f251f7","slug":"aicar-ribotide","display_name":"5-Aminoimidazole-4-carboxamide ribonucleotide","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"6109c7d6-21e2-5aab-8369-ac56537810dc","stable_key":"ec174d5a-4903-5745-8646-df0e9d4265e8:aldh1l1-aicar-accumulation-event","event_type":"biochemical_relationship","label":"Disposing of folate-bound carbon can slow a purine-building step.","description":"Ectopic ALDH1L1 expression in HuH-7 cells increased ZMP/AICAR ribotide, consistent with reduced formyl-donor availability for ATIC.","status":"provisional","compartment":{"slug":"cytosol","display_name":"Cytosol"},"participants":[{"entity":{"id":"ec73b364-a2ea-5c4a-bcea-a54aeebf57d1","slug":"10-formyltetrahydrofolate","display_name":"10-Formyltetrahydrofolate","entity_type_key":"small_molecule"},"role":"shared substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9dec8ed2-6916-5967-8a8c-243dd6d4d5f1","slug":"atic","display_name":"Human bifunctional ATIC","entity_type_key":"protein"},"role":"competing formyl-transfer enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"546aed58-bcd0-5ed1-8b43-c196155dcbac","slug":"aldh1l1","display_name":"Human ALDH1L1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4af06f63-38d1-5e5a-be55-69db44f251f7","slug":"aicar-ribotide","display_name":"5-Aminoimidazole-4-carboxamide ribonucleotide","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Stable expression and metabolomics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Engineered ALDH1L1 expression.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Overexpression in one cancer line; substrate competition is the study interpretation.","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":"Disposing of folate-bound carbon can slow a purine-building step.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HuH-7 hepatocellular carcinoma cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"e45e9c3a-06dd-5a99-88ea-5c2fbb0975cc","evidence_kind":"source_excerpt","locator":"Lines 1072-1082","start_line":1072,"end_line":1082,"excerpt":"### aldh1l1-aicar-accumulation\nEctopic ALDH1L1 expression in HuH-7 cells increased ZMP/AICAR ribotide, consistent with reduced formyl-donor availability for ATIC.\nCondition category: normal\nnutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Disposing of folate-bound carbon can slow a purine-building step.\norganism: Homo sapiens\ntissue_or_cell_type: HuH-7 hepatocellular carcinoma cells\nexperimental_model: Stable expression and metabolomics\nlimitations: Overexpression in one cancer line; substrate competition is the study interpretation.\nexposure: Engineered ALDH1L1 expression.\n[sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5","model_system":"Stable expression and metabolomics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5","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. 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