{"id":"182c0b05-4f71-5285-9087-5415c843e44b","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-cons-nnmt-sam-low-methionine","predicate":"decreases","statement":"In 769P cells cultured with 10 micromolar methionine, NNMT overexpression significantly lowered SAM relative to control cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f2686a69-1e93-5492-8f42-1e7ba667d3a7","mechanism_event_label":"SAM fell when these NNMT-rich cancer cells were cultured with less methionine.","subject":{"id":"68273ca3-19da-57e0-85bb-2f1245928df5","slug":"nnmt","display_name":"Human NNMT","entity_type_key":"protein"},"object":{"id":"7e7b818f-78ef-5a36-83d4-73d46ad20054","slug":"cellular-sam-concentration","display_name":"Cellular S-adenosylmethionine concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f2686a69-1e93-5492-8f42-1e7ba667d3a7","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:b3-cons-nnmt-sam-low-methionine-event","event_type":"biochemical_relationship","label":"SAM fell when these NNMT-rich cancer cells were cultured with less methionine.","description":"In 769P cells cultured with 10 micromolar methionine, NNMT overexpression significantly lowered SAM relative to control cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"68273ca3-19da-57e0-85bb-2f1245928df5","slug":"nnmt","display_name":"Human NNMT","entity_type_key":"protein"},"role":"enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"culture_nutrient","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"role":"methyl_donor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7e7b818f-78ef-5a36-83d4-73d46ad20054","slug":"cellular-sam-concentration","display_name":"Cellular S-adenosylmethionine concentration","entity_type_key":"cellular_process"},"role":"outcome","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-consumption-sources/nnmt2013.txt\", \"locator\": \"Full text, normalized paragraph 24\", \"start_char\": 12788, \"end_char\": 14928, \"file_sha256\": \"7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca\", \"text_sha256\": \"760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Targeted LC-MS metabolomics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NNMT overexpression versus GFP/inactive Y20A controls in 10 micromolar methionine medium","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. Low medium methionine is an experimental exposure, not diagnosed human methionine or niacin deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"SAM fell when these NNMT-rich cancer cells were cultured with less methionine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human 769P renal carcinoma cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b88b1a96-ff12-56d8-ad4a-a9421f2e6e3d","evidence_kind":"source_excerpt","locator":"Lines 789-801","start_line":789,"end_line":801,"excerpt":"### b3-cons-nnmt-sam-low-methionine\nIn 769P cells cultured with 10 micromolar methionine, NNMT overexpression significantly lowered SAM relative to control cells.\nCondition category: normal\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: SAM fell when these NNMT-rich cancer cells were cultured with less methionine.\norganism: Human\ntissue_or_cell_type: Human 769P renal carcinoma cells\nexperimental_model: Targeted LC-MS metabolomics\nlimitations: Engineered human cancer-cell culture, not healthy-human niacin repletion. SAM consumption does not establish systemic methyl depletion or a need for folate/B12 supplements. Low medium methionine is an experimental exposure, not diagnosed human methionine or niacin deficiency.\nexposure: NNMT overexpression versus GFP/inactive Y20A controls in 10 micromolar methionine medium\ncross_nutrient: true\nevidence_span: {\"source_cache\": \"artifacts/niacin-consumption-sources/nnmt2013.txt\", \"locator\": \"Full text, normalized paragraph 24\", \"start_char\": 12788, \"end_char\": 14928, \"file_sha256\": \"7d88fd656ba772962185234a9bd021e40a9b83f9156db836f723eba06b68acca\", \"text_sha256\": \"760641ee47babbc4c1261afe881ea4baa14ae9032d0538bd467c9957224059f7\"}\n[b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204","model_system":"Targeted LC-MS metabolomics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b3-cons-nnmt2013] NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. (2013). https://pubmed.ncbi.nlm.nih.gov/23455543/ DOI: 10.1038/nchembio.1204","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a62b7b5b-786a-57e9-85e9-67c6912a5054","stable_key":"import-a9dd23c6-978a-5755-8bd8-f29bd1fe0cda","title":"Niacin: NAD metabolism, 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":"a8cac59639322f74812ce12eef338c2f6c385c04cc4af6ab511fc7c972f0c2e6","revision_id":"bec8fc45-12e7-5f75-a814-5d72ed015d01","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}