{"id":"908ec657-5bf1-5573-ba89-60fd79065c48","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-thdp-feedback-on-tpk","predicate":"inhibits","statement":"Accumulated ThDP inhibited the forward reaction of purified mouse TPK1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ce3e19d5-7f4f-5ab0-ace7-0f38d16138af","mechanism_event_label":"B1 activation has product feedback even when ATP and magnesium are supplied.","subject":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"object":{"id":"692f8f7a-32ba-58ff-9242-0784d97f9bff","slug":"mouse-tpk1","display_name":"Mouse thiamine pyrophosphokinase 1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ce3e19d5-7f4f-5ab0-ace7-0f38d16138af","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:mg-thdp-feedback-on-tpk-event","event_type":"biochemical_relationship","label":"B1 activation has product feedback even when ATP and magnesium are supplied.","description":"Accumulated ThDP inhibited the forward reaction of purified mouse TPK1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"assay cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"58b974f1-d389-5bf6-81cd-889c44442c42","slug":"atp","display_name":"ATP","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"36b7c3eb-068b-500f-af1c-078829df1ecc","slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"692f8f7a-32ba-58ff-9242-0784d97f9bff","slug":"mouse-tpk1","display_name":"Mouse thiamine pyrophosphokinase 1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified recombinant mouse TPK1; forward and reverse reaction kinetics.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Product inhibition is a separate limit from Mg shortage.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"B1 activation has product feedback even when ATP and magnesium are supplied.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified recombinant enzyme","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8727b696-58df-5a22-ac8e-4f1cb887ba5a","evidence_kind":"source_excerpt","locator":"Lines 529-539","start_line":529,"end_line":539,"excerpt":"### mg-thdp-feedback-on-tpk\nAccumulated ThDP inhibited the forward reaction of purified mouse TPK1.\nCondition category: normal\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: B1 activation has product feedback even when ATP and magnesium are supplied.\norganism: Mus musculus\ntissue_or_cell_type: Purified recombinant enzyme\nexperimental_model: Purified recombinant mouse TPK1; forward and reverse reaction kinetics.\nlimitations: Product inhibition is a separate limit from Mg shortage.\ncross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.\n[sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071","model_system":"Purified recombinant mouse TPK1; forward and reverse reaction kinetics.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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