{"id":"fd9959d6-d5f9-56f8-8e81-8e058d98019b","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-gut-transporter-stress","predicate":"loss_increased","statement":"CRT loss increased epithelial glycolytic stress and was accompanied by actin mislocalization and leaky junctions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d0f87975-145f-5351-860e-26d1575fff02","mechanism_event_label":"The transporter defect changed both energy handling and the cell structures that seal the barrier.","subject":{"id":"75fe55a3-ff87-5cbd-bb76-e808421fa627","slug":"slc6a8","display_name":"Human creatine transporter CRT / SLC6A8","entity_type_key":"protein"},"object":{"id":"95ba1726-63c4-5c24-b06f-5d116ab7266f","slug":"intestinal-epithelial-glycolytic-stress","display_name":"Intestinal epithelial glycolytic stress","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d0f87975-145f-5351-860e-26d1575fff02","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-gut-transporter-stress-event","event_type":"biochemical_relationship","label":"The transporter defect changed both energy handling and the cell structures that seal the barrier.","description":"CRT loss increased epithelial glycolytic stress and was accompanied by actin mislocalization and leaky junctions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"75fe55a3-ff87-5cbd-bb76-e808421fa627","slug":"slc6a8","display_name":"Human creatine transporter CRT / SLC6A8","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"95ba1726-63c4-5c24-b06f-5d116ab7266f","slug":"intestinal-epithelial-glycolytic-stress","display_name":"Intestinal epithelial glycolytic stress","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/creatine-research/32433978.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887\", \"start_char\": 0, \"end_char\": 2283, \"text_sha256\": \"1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transporter manipulation, intestinal organoids and human biopsy comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Creatine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"creatine","display_name":"Creatine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human T84 cells, mouse organoids and human IBD biopsies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The transporter defect changed both energy handling and the cell structures that seal the barrier.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. (2020). https://pubmed.ncbi.nlm.nih.gov/32433978/ DOI: 10.1053/j.gastro.2020.05.033","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Intestinal epithelium and tight junctions","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"6de6038f-d329-5ba9-b8ab-f6265e6c198b","evidence_kind":"source_excerpt","locator":"Lines 659-670","start_line":659,"end_line":670,"excerpt":"### creatine-gut-transporter-stress\nCRT loss increased epithelial glycolytic stress and was accompanied by actin mislocalization and leaky junctions.\nCondition category: machinery_impairment\nnutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The transporter defect changed both energy handling and the cell structures that seal the barrier.\norganism: Human T84 cells, mouse organoids and human IBD biopsies\ntissue_or_cell_type: Intestinal epithelium and tight junctions\nexperimental_model: Transporter manipulation, intestinal organoids and human biopsy comparison\nlimitations: Causal epithelial experiments and observational human expression findings are distinct; no human creatine treatment outcome was tested.\nexposure: CRT knockdown/overexpression; transporter-deficient organoids; 30 Crohn disease, 27 ulcerative colitis and 30 control biopsies\nevidence_span: {\"source_cache\": \"artifacts/creatine-research/32433978.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887\", \"start_char\": 0, \"end_char\": 2283, \"text_sha256\": \"1733708b77e75d099fa25665b9b9a9aa0af72143c985b6f0f2b931fb8f4c0887\"}\n[creatine-p32433978] Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. 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