{"id":"813732ae-d015-5382-9fce-68d4649d5b3b","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-pc-islet-gsh","predicate":"supports","statement":"Genetic depletion of PC in human islets reduced glutathione and the GSH/GSSG ratio under nitrosative stress.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"94ab0bf5-ceb5-57d8-b66d-befbcd62c22e","mechanism_event_label":"PC connects carbon metabolism to the cell’s ability to maintain glutathione.","subject":{"id":"b84a1471-7246-543a-8f35-2bedbca6bf0b","slug":"pc","display_name":"Human pyruvate carboxylase / PC","entity_type_key":"protein"},"object":{"id":"177cb3e2-bbc6-5036-9d9a-0778624018a9","slug":"human-islet-glutathione-synthesis","display_name":"Human pancreatic-islet glutathione synthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"94ab0bf5-ceb5-57d8-b66d-befbcd62c22e","stable_key":"08ce9896-9d1c-5bbf-b705-5bfe771091d5:b7-pc-islet-gsh-event","event_type":"biochemical_relationship","label":"PC connects carbon metabolism to the cell’s ability to maintain glutathione.","description":"Genetic depletion of PC in human islets reduced glutathione and the GSH/GSSG ratio under nitrosative stress.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"affected antioxidant","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1d9b9d7b-3fdf-57af-b9dd-00194fa1de9e","slug":"oxidized-glutathione","display_name":"GSSG","entity_type_key":"small_molecule"},"role":"redox partner","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"37a8e96b-f95b-5ba7-a0bc-8ed3cfaf5fd8","slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"},"role":"PC cofactor context","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b84a1471-7246-543a-8f35-2bedbca6bf0b","slug":"pc","display_name":"Human pyruvate carboxylase / PC","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"177cb3e2-bbc6-5036-9d9a-0778624018a9","slug":"human-islet-glutathione-synthesis","display_name":"Human pancreatic-islet glutathione synthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/biotin-research/34818536.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"48bcb3951c9b630862fdda839e0a54b80abe9e2cf2e79d0bfb7547e2af317523\", \"start_char\": 35800, \"end_char\": 36138, \"text_sha256\": \"b1dd7e5022ba64d19114d853d2f75c43e061cdca76e1938e95c19379e96c3933\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Glucose tracer, PC knockdown and nitric-oxide donor exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Genetic perturbation of PC in isolated islets is not dietary biotin depletion or evidence that biotin supplements raise glutathione in replete people.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Biotin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"biotin","display_name":"Biotin","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"PC connects carbon metabolism to the cell’s ability to maintain glutathione.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Primary human pancreatic islets","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"0af5b05a-c3e9-5a96-9f0e-135acb12258b","evidence_kind":"source_excerpt","locator":"Lines 871-882","start_line":871,"end_line":882,"excerpt":"### b7-pc-islet-gsh\nGenetic depletion of PC in human islets reduced glutathione and the GSH/GSSG ratio under nitrosative stress.\nCondition category: machinery_impairment\nnutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: PC connects carbon metabolism to the cell’s ability to maintain glutathione.\norganism: Homo sapiens\ntissue_or_cell_type: Primary human pancreatic islets\nexperimental_model: Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress\nlimitations: Genetic perturbation of PC in isolated islets is not dietary biotin depletion or evidence that biotin supplements raise glutathione in replete people.\nexposure: Glucose tracer, PC knockdown and nitric-oxide donor exposure\nevidence_span: {\"source_cache\": \"artifacts/biotin-research/34818536.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"48bcb3951c9b630862fdda839e0a54b80abe9e2cf2e79d0bfb7547e2af317523\", \"start_char\": 35800, \"end_char\": 36138, \"text_sha256\": \"b1dd7e5022ba64d19114d853d2f75c43e061cdca76e1938e95c19379e96c3933\"}\n[b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037","model_system":"Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"9608806b-adb6-5a35-b042-057147135642","stable_key":"import-08ce9896-9d1c-5bbf-b705-5bfe771091d5","title":"Biotin: carboxylases, recycling, 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":"a05b23a45e0813ba2fcda0027e3f5d9d58b82858f8dd8598ffb7aca17e942a38","revision_id":"e0d0c2a2-e9e2-55dd-b467-41c22ba960d4","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}