{"id":"9f84f063-5b4e-5997-8747-848abf014c4d","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-tnap-pcr-hydrolysis","predicate":"hydrolyzes","statement":"TNAP localized to thermogenic adipocyte mitochondria and hydrolyzed phosphocreatine to support the futile creatine cycle.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"684c6af0-495f-5b20-8c5d-2497a3298b81","mechanism_event_label":"This phosphatase releases the stored phosphate without making ATP, allowing continued fuel use and heat production.","subject":{"id":"a5121afd-8f8d-5584-9eb5-f8243cd198a9","slug":"mouse-alpl","display_name":"Mouse tissue-nonspecific alkaline phosphatase / Alpl","entity_type_key":"protein"},"object":{"id":"c081984a-e118-582f-ac46-6a767f8f0bf2","slug":"phosphocreatine","display_name":"Phosphocreatine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"684c6af0-495f-5b20-8c5d-2497a3298b81","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-tnap-pcr-hydrolysis-event","event_type":"biochemical_relationship","label":"This phosphatase releases the stored phosphate without making ATP, allowing continued fuel use and heat production.","description":"TNAP localized to thermogenic adipocyte mitochondria and hydrolyzed phosphocreatine to support the futile creatine cycle.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9f5df558-ed3d-5cda-b5ca-0f90f7aa6a8c","slug":"creatine","display_name":"Creatine","entity_type_key":"small_molecule"},"role":"cycle_product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b28dfc54-a5ef-5f9e-ac1f-890b68e58dc3","slug":"inorganic-phosphate","display_name":"Inorganic phosphate","entity_type_key":"chemical_species"},"role":"hydrolysis_product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a5121afd-8f8d-5584-9eb5-f8243cd198a9","slug":"mouse-alpl","display_name":"Mouse tissue-nonspecific alkaline phosphatase / Alpl","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"c081984a-e118-582f-ac46-6a767f8f0bf2","slug":"phosphocreatine","display_name":"Phosphocreatine","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/creatine-research/33981039.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca\", \"start_char\": 0, \"end_char\": 1400, \"text_sha256\": \"915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"TNAP inhibition and adipocyte Alpl deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans.","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":"Mouse thermogenic adipocytes and mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"This phosphatase releases the stored phosphate without making ATP, allowing continued fuel use and heat production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. (2021). https://pubmed.ncbi.nlm.nih.gov/33981039/ DOI: 10.1038/s41586-021-03533-z","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Adipocyte mitochondria","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"724be53e-f2ff-5f59-bd74-ab739ee7013f","evidence_kind":"source_excerpt","locator":"Lines 503-514","start_line":503,"end_line":514,"excerpt":"### creatine-tnap-pcr-hydrolysis\nTNAP localized to thermogenic adipocyte mitochondria and hydrolyzed phosphocreatine to support the futile creatine cycle.\nCondition category: normal\nnutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This phosphatase releases the stored phosphate without making ATP, allowing continued fuel use and heat production.\norganism: Mouse thermogenic adipocytes and mice\ntissue_or_cell_type: Adipocyte mitochondria\nexperimental_model: Phosphatase biochemistry, mitochondrial inhibition and adipocyte gene deletion\nlimitations: Mouse mechanism; it does not establish that creatine supplements cause weight loss in humans.\nexposure: TNAP inhibition and adipocyte Alpl deletion\nevidence_span: {\"source_cache\": \"artifacts/creatine-research/33981039.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca\", \"start_char\": 0, \"end_char\": 1400, \"text_sha256\": \"915403423e16b5e0e5db70e99ebc6518e612bc9ef69ceb1e25da3074a8410dca\"}\n[creatine-p33981039] Mitochondrial TNAP controls thermogenesis by hydrolysis of phosphocreatine. 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