{"id":"6909e760-e000-55e2-aff6-3c2b996a8109","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-chac1-gsh","predicate":"depletes_on_overexpression","statement":"CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8d2cf5b3-247b-52cc-9c3e-b6f10dbe97e3","mechanism_event_label":"Low glutathione can reflect increased breakdown, not just poor supply.","subject":{"id":"dd196d1a-623b-58f4-9662-947cd5f392c7","slug":"chac1","display_name":"Human glutathione-specific gamma-glutamylcyclotransferase CHAC1","entity_type_key":"protein"},"object":{"id":"5e8dd2eb-2ad7-519b-a0a1-0ff9ffa705da","slug":"cellular-glutathione-pool","display_name":"Cellular reduced-glutathione pool","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"8d2cf5b3-247b-52cc-9c3e-b6f10dbe97e3","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-chac1-gsh-event","event_type":"biochemical_relationship","label":"Low glutathione can reflect increased breakdown, not just poor supply.","description":"CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"degraded_substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"dd196d1a-623b-58f4-9662-947cd5f392c7","slug":"chac1","display_name":"Human glutathione-specific gamma-glutamylcyclotransferase CHAC1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5e8dd2eb-2ad7-519b-a0a1-0ff9ffa705da","slug":"cellular-glutathione-pool","display_name":"Cellular reduced-glutathione pool","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glutathione-research/25931127.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1\", \"start_char\": 0, \"end_char\": 1504, \"text_sha256\": \"a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human promoter reporters, binding assays and overexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"ER stress, ATF4 and CHAC1 expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Glutathione research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Low glutathione can reflect increased breakdown, not just poor supply.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"HEK293 and U2OS cells","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b676ddd9-7fec-5017-a63d-7991ded9f295","evidence_kind":"source_excerpt","locator":"Lines 580-591","start_line":580,"end_line":591,"excerpt":"### glutathione-chac1-gsh\nCHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion.\nCondition category: normal\nnutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Low glutathione can reflect increased breakdown, not just poor supply.\norganism: Human\ntissue_or_cell_type: HEK293 and U2OS cells\nexperimental_model: Human promoter reporters, binding assays and overexpression\nlimitations: Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.\nexposure: ER stress, ATF4 and CHAC1 expression\nevidence_span: {\"source_cache\": \"artifacts/glutathione-research/25931127.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1\", \"start_char\": 0, \"end_char\": 1504, \"text_sha256\": \"a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1\"}\n[glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. 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