{"id":"7178a7d1-1f66-5869-bc8b-3a8cabcdb569","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-cd73-negative","predicate":"poorly_processes","statement":"Recombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"aa484eb2-ce2e-5522-9338-18bef700d044","mechanism_event_label":"A later direct assay challenged the proposed precursor-processing enzyme.","subject":{"id":"3e700717-6e07-59d4-96ec-3692c77c6266","slug":"nt5e","display_name":"Human ecto-5-prime-nucleotidase / CD73 / NT5E","entity_type_key":"protein"},"object":{"id":"d1c59139-db61-5fa0-a25d-40c3e625152e","slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"aa484eb2-ce2e-5522-9338-18bef700d044","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-cd73-negative-event","event_type":"observed_relationship","label":"A later direct assay challenged the proposed precursor-processing enzyme.","description":"Recombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3e700717-6e07-59d4-96ec-3692c77c6266","slug":"nt5e","display_name":"Human ecto-5-prime-nucleotidase / CD73 / NT5E","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d1c59139-db61-5fa0-a25d-40c3e625152e","slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human recombinant enzyme; biochemical substrate assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation.","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":"A later direct assay challenged the proposed precursor-processing enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c97c8050-0466-5f13-9363-fb3a025f4569","evidence_kind":"source_excerpt","locator":"Lines 236-242","start_line":236,"end_line":242,"excerpt":"## nad-plus-cd73-negative\nA later direct assay challenged the proposed precursor-processing enzyme.\nRecombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays.\nModel: Human recombinant enzyme; biochemical substrate assays.\nLimitations: Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation.\nEvidence access: Primary full text\nExtracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9","model_system":"Human recombinant enzyme; biochemical substrate assays.","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. Not publisher full text.","file_path":"","sha256":"9f5324d0d652c80ad630b3100e28ce34cd2ce260ea2e1324332a4262ce72ae09","revision_id":"0e07909c-e8bc-5950-bafc-61371d9d6412","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"7e02254f-3ded-5657-ab31-47fa6e7c73ff","title":"Does human CD73 process extracellular NAD/NMN for NAD salvage?","kind":"contradiction","status":"open","why":"The 2013 cellular study assigns CD73 a precursor-processing role and finds NMN rescue sensitive to CD73 inhibition or silencing. The 2020 recombinant-enzyme and knockout study challenges both efficient catalysis and CD73 necessity. This is a disagreement about a mechanism, not a corrected draft label.","resolution":"Keep the positive cellular dependency and negative biochemical/knockout results with their models. Direct catalytic assignment and general necessity remain unresolved across these systems; indirect effects, preparation, residual enzymes and alternative routes are testable explanations, not established resolutions.","created_at":"2026-09-19 08:57:32","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/7e02254f-3ded-5657-ab31-47fa6e7c73ff","sides":[{"conflict_id":"7e02254f-3ded-5657-ab31-47fa6e7c73ff","ordinal":0,"label":"Reported CD73-dependent NMN rescue","revision_id":"0e07909c-e8bc-5950-bafc-61371d9d6412","start_line":228,"end_line":234,"quote":"## nad-plus-cd73-positive\nOne study found that CD73 helped cells use an outside NAD precursor.\nCD73 silencing or pharmacological inhibition reduced NMN-supported survival after NAMPT inhibition in human tumor cells; the authors assigned CD73 a role in converting extracellular NMN to NR.\nModel: Human tumor-cell CD73 overexpression/silencing and FK866 experiments.\nLimitations: Mechanistic assignment is disputed by the later human recombinant-enzyme and knockout study. Primary abstract accessed here; direct catalytic attribution is retained as reported.\nEvidence access: Primary abstract\nCD73 protein as a source of extracellular precursors for sustained NAD+ biosynthesis in FK866-treated tumor cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23880765/ · DOI 10.1074/jbc.M113.470435","source_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","source_title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","claim_ids":["45fb4e42-a5bb-5d50-948a-08535052e8ca"]},{"conflict_id":"7e02254f-3ded-5657-ab31-47fa6e7c73ff","ordinal":1,"label":"Recombinant human enzyme challenge","revision_id":"0e07909c-e8bc-5950-bafc-61371d9d6412","start_line":236,"end_line":242,"quote":"## nad-plus-cd73-negative\nA later direct assay challenged the proposed precursor-processing enzyme.\nRecombinant human CD73 did not process NAD+ and processed NMN poorly in the reported biochemical assays.\nModel: Human recombinant enzyme; biochemical substrate assays.\nLimitations: Do not erase the earlier cellular result. Preparation, assay sensitivity and indirect cellular effects require reconciliation.\nEvidence access: Primary full text\nExtracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9","source_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","source_title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","claim_ids":["7178a7d1-1f66-5869-bc8b-3a8cabcdb569"]},{"conflict_id":"7e02254f-3ded-5657-ab31-47fa6e7c73ff","ordinal":2,"label":"CD73-independent cellular rescue","revision_id":"0e07909c-e8bc-5950-bafc-61371d9d6412","start_line":244,"end_line":250,"quote":"## nad-plus-cd73-knockout\nCells could still use outside precursor material without CD73.\nCD73 knockout did not prevent human cancer cells from using extracellular NAD+ or NMN to restore intracellular NAD+ under the tested conditions.\nModel: Human cancer-cell CRISPR knockout and precursor supplementation.\nLimitations: Does not identify a universal alternative uptake route or prove intact NAD crossed the plasma membrane.\nEvidence access: Primary full text\nExtracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31959836/ · DOI 10.1038/s41598-020-57506-9","source_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","source_title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","claim_ids":["08894837-ea67-54c2-a0ce-ddbba6dccf32"]}]}],"corrections":[],"research":null}