{"id":"ad642c7d-99b3-513e-b35d-6d107696ca24","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-p5cs-nadph","predicate":"supports","statement":"P5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f1924625-b34d-5849-ae25-5bf7da195cb4","mechanism_event_label":"A niacin-derived electron donor participates upstream of citrulline.","subject":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"object":{"id":"39697257-d4c2-5f40-9eb1-8f230a5ac764","slug":"aldh18a1","display_name":"Human pyrroline-5-carboxylate synthase / ALDH18A1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"f1924625-b34d-5849-ae25-5bf7da195cb4","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-p5cs-nadph-event","event_type":"biochemical_relationship","label":"A niacin-derived electron donor participates upstream of citrulline.","description":"P5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7da684a4-2641-5bc6-93ae-8c6aa384e487","slug":"glutamate","display_name":"L-Glutamate","entity_type_key":"small_molecule"},"role":"substrate","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":"energy_substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"reducing_cosubstrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"39697257-d4c2-5f40-9eb1-8f230a5ac764","slug":"aldh18a1","display_name":"Human pyrroline-5-carboxylate synthase / ALDH18A1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/citrulline-research/11092761.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2\", \"start_char\": 0, \"end_char\": 1688, \"text_sha256\": \"09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Patient genetics and recombinant variant expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ALDH18A1 R84Q compared with wild-type isoforms","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Citrulline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"citrulline","display_name":"L-Citrulline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human, two siblings and mammalian expression systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A niacin-derived electron donor participates upstream of citrulline.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondrial P5CS and circulating amino acids","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"375cff6b-ac55-5b98-bf18-e0e74d3a28e6","evidence_kind":"source_excerpt","locator":"Lines 307-318","start_line":307,"end_line":318,"excerpt":"### citrulline-p5cs-nadph\nP5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis.\nCondition category: normal\nnutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A niacin-derived electron donor participates upstream of citrulline.\norganism: Human, two siblings and mammalian expression systems\ntissue_or_cell_type: Mitochondrial P5CS and circulating amino acids\nexperimental_model: Patient genetics and recombinant variant expression\nlimitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.\nexposure: ALDH18A1 R84Q compared with wild-type isoforms\nevidence_span: {\"source_cache\": \"artifacts/citrulline-research/11092761.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2\", \"start_char\": 0, \"end_char\": 1688, \"text_sha256\": \"09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2\"}\n[citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853","model_system":"Patient genetics and recombinant variant expression","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"112fd375-aa2a-59d2-8afd-6b2849bb79ee","stable_key":"import-a9828b14-fbd7-57bf-9e01-0d52d1b42a1f","title":"Citrulline: arginine recycling, nitrogen disposal and nutrient connections (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":"3720442dbabc28cacefd2145c7c97bfb937df26dca8527fde219ecd3735ed558","revision_id":"41ac8493-b004-59d7-99b3-8a3ca7163d3a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}