{"id":"4d58e1d7-9561-50fd-9be5-888587cb630f","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-p5cs-reaction","predicate":"converts_glutamate_to","statement":"Human P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"580f64ba-f269-521c-9b1d-5d49309db2c9","mechanism_event_label":"This supplies a precursor route connected to ornithine and arginine production.","subject":{"id":"39697257-d4c2-5f40-9eb1-8f230a5ac764","slug":"aldh18a1","display_name":"Human pyrroline-5-carboxylate synthase / ALDH18A1","entity_type_key":"protein"},"object":{"id":"cbf8b66e-3d66-53f0-9c21-bc9c014131e7","slug":"pyrroline-5-carboxylate","display_name":"Delta-1-pyrroline-5-carboxylate / P5C","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"580f64ba-f269-521c-9b1d-5d49309db2c9","stable_key":"a9828b14-fbd7-57bf-9e01-0d52d1b42a1f:citrulline-p5cs-reaction-event","event_type":"biochemical_relationship","label":"This supplies a precursor route connected to ornithine and arginine production.","description":"Human P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry.","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":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"cbf8b66e-3d66-53f0-9c21-bc9c014131e7","slug":"pyrroline-5-carboxylate","display_name":"Delta-1-pyrroline-5-carboxylate / P5C","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"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":"This supplies a precursor route connected to ornithine and arginine production.","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":"621aa18d-eb3d-51ba-b90e-24a17c41ee69","evidence_kind":"source_excerpt","locator":"Lines 294-305","start_line":294,"end_line":305,"excerpt":"### citrulline-p5cs-reaction\nHuman P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry.\nCondition category: normal\nnutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: This supplies a precursor route connected to ornithine and arginine production.\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. 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