{"id":"38930f61-cfa0-5d4a-af0b-dd74fede704a","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-tnap-pocket-thermogenesis","predicate":"glycerol_pocket_supports","statement":"The TNAP glycerol pocket was required for TNAP-driven thermogenesis through the futile creatine cycle in the tested systems.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"611df26d-d838-565c-9a6f-763ca68bca0b","mechanism_event_label":"The same phosphatase needs a regulatory pocket to support this heat-producing pathway.","subject":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"object":{"id":"99246e86-63e5-544b-bcba-43869401ebef","slug":"adipocyte-thermogenesis","display_name":"Heat production and energy expenditure by thermogenic adipocytes","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"611df26d-d838-565c-9a6f-763ca68bca0b","stable_key":"44737fa3-b335-53f4-a644-b9878d4416ac:creatine-tnap-pocket-thermogenesis-event","event_type":"biochemical_relationship","label":"The same phosphatase needs a regulatory pocket to support this heat-producing pathway.","description":"The TNAP glycerol pocket was required for TNAP-driven thermogenesis through the futile creatine cycle in the tested systems.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"af8eada2-0a93-5943-b1d9-8ee9ac68f8ee","slug":"glycerol","display_name":"Glycerol","entity_type_key":"small_molecule"},"role":"allosteric_regulator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9f5df558-ed3d-5cda-b5ca-0f90f7aa6a8c","slug":"creatine","display_name":"Creatine","entity_type_key":"small_molecule"},"role":"cycle_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c081984a-e118-582f-ac46-6a767f8f0bf2","slug":"phosphocreatine","display_name":"Phosphocreatine","entity_type_key":"small_molecule"},"role":"cycle_intermediate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"99246e86-63e5-544b-bcba-43869401ebef","slug":"adipocyte-thermogenesis","display_name":"Heat production and energy expenditure by thermogenic adipocytes","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/creatine-research/42020733.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd\", \"start_char\": 0, \"end_char\": 1255, \"text_sha256\": \"232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Structural, biochemical, cellular, physiological and human genetic experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Glycerol binding and glycerol-pocket disruption","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease.","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":"TNAP experimental systems, mice and human variant analyses","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The same phosphatase needs a regulatory pocket to support this heat-producing pathway.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. (2026). https://pubmed.ncbi.nlm.nih.gov/42020733/ DOI: 10.1038/s41586-026-10396-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Thermogenic adipocytes, osteoblasts and purified protein","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"26b8f9f7-15b7-5fdf-b912-3b0be2062921","evidence_kind":"source_excerpt","locator":"Lines 555-566","start_line":555,"end_line":566,"excerpt":"### creatine-tnap-pocket-thermogenesis\nThe TNAP glycerol pocket was required for TNAP-driven thermogenesis through the futile creatine cycle in the tested systems.\nCondition category: normal\nnutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The same phosphatase needs a regulatory pocket to support this heat-producing pathway.\norganism: TNAP experimental systems, mice and human variant analyses\ntissue_or_cell_type: Thermogenic adipocytes, osteoblasts and purified protein\nexperimental_model: Structural, biochemical, cellular, physiological and human genetic experiments\nlimitations: Published 2026; model-specific thermogenesis and mineralization findings do not establish a dietary glycerol or creatine treatment for bone disease.\nexposure: Glycerol binding and glycerol-pocket disruption\nevidence_span: {\"source_cache\": \"artifacts/creatine-research/42020733.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd\", \"start_char\": 0, \"end_char\": 1255, \"text_sha256\": \"232795a0a16f2f2445cd43c34e4542fb2470eefb41f72fa9dc655991dbd772fd\"}\n[creatine-p42020733] Glycerol-driven TNAP activation in thermogenesis and mineralization. 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