{"id":"9a69faf2-af11-5ae8-a093-15dfa72c6ac1","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-ldh-redox","predicate":"regenerates","statement":"In the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4b3953a6-5001-53ad-9d1e-c2c351f7b311","mechanism_event_label":"An electron acceptor can restore NAD without making new NAD molecules.","subject":{"id":"feca41d0-c968-535e-9237-bd380dc918b5","slug":"human-lactate-dehydrogenase-activity","display_name":"Human lactate dehydrogenase activity","entity_type_key":"cellular_process"},"object":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"4b3953a6-5001-53ad-9d1e-c2c351f7b311","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-ldh-redox-event","event_type":"observed_relationship","label":"An electron acceptor can restore NAD without making new NAD molecules.","description":"In the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"feca41d0-c968-535e-9237-bd380dc918b5","slug":"human-lactate-dehydrogenase-activity","display_name":"Human lactate dehydrogenase activity","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"91e6d4f5-fba1-542d-b68a-57cc28e1e425","slug":"pyruvate","display_name":"Pyruvate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9fbf2e03-16a9-5ca7-965c-0bfc07ca24da","slug":"nadh","display_name":"NADH","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"5ebd9a7c-b151-5b70-b70d-7d33067d4ebf","slug":"lactate","display_name":"L-Lactate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human cancer-cell nutrient manipulation and NAD+/NADH measurements.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Reaction-level LDH activity is recorded without assigning an untested isoform.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"An electron acceptor can restore NAD without making new NAD molecules.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"84763b05-9f11-5948-aed6-3374f9134579","evidence_kind":"source_excerpt","locator":"Lines 348-354","start_line":348,"end_line":354,"excerpt":"## nad-plus-ldh-redox\nAn electron acceptor can restore NAD without making new NAD molecules.\nIn the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition.\nModel: Human cancer-cell nutrient manipulation and NAD+/NADH measurements.\nLimitations: Reaction-level LDH activity is recorded without assigning an untested isoform.\nEvidence access: Primary full text\nEnvironment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006","model_system":"Human cancer-cell nutrient manipulation and NAD+/NADH measurements.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f59aa302-d463-5462-876f-e21e64861eac","stable_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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