{"id":"eacf7f2b-839e-5e0c-a52c-c32df41360a5","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-zinc-cannot-bypass-znt-loss","predicate":"fails_to_restore_activity_of","statement":"Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"ff62ee86-7493-5fb2-b77b-ead077561511","mechanism_event_label":"More available zinc did not bypass missing enzyme-loading machinery.","subject":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"object":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ff62ee86-7493-5fb2-b77b-ead077561511","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-zinc-cannot-bypass-znt-loss-event","event_type":"biochemical_relationship","label":"More available zinc did not bypass missing enzyme-loading machinery.","description":"Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a483be20-7a24-5fca-8016-0b0e2032fdba","slug":"slc30a5","display_name":"Human zinc transporter 5 / ZnT5","entity_type_key":"protein"},"role":"transporter_component","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0bb32d07-f10b-55f5-b4ae-157f25baceca","slug":"slc30a6","display_name":"Human zinc transporter 6 / ZnT6","entity_type_key":"protein"},"role":"transporter_component","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"39936fe1-d2f5-5328-ae8b-fa92e57da591","slug":"slc30a7","display_name":"Human zinc transporter 7 / ZnT7","entity_type_key":"protein"},"role":"parallel_transporter","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"delivered_cofactor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"6a41210b-22c9-51f0-82ab-7f2842953269","slug":"chicken-dt40-znt5-znt6-znt7-null","display_name":"Chicken DT40 cells lacking ZnT5, ZnT6 and ZnT7","entity_type_key":"cell_type"},"role":"impaired_cell_model","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Gallus gallus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More available zinc did not bypass missing enzyme-loading machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Chicken DT40 early secretory pathway","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":"ffd2ff0f-af12-55fb-a8eb-231151272c0d","evidence_kind":"source_excerpt","locator":"Lines 781-792","start_line":781,"end_line":792,"excerpt":"### zinc-enz-zinc-cannot-bypass-znt-loss\nExtracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.\nCondition category: machinery_impairment\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More available zinc did not bypass missing enzyme-loading machinery.\norganism: Gallus gallus\ntissue_or_cell_type: Chicken DT40 early secretory pathway\nexperimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation\nlimitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.\nexposure: Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract.\ncross_nutrient: false\n[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173","model_system":"Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, 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. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}