{"id":"8357e2d4-40de-5c82-b0b2-5ee259e933cf","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-gss-pyroglutamate","predicate":"is_associated_with","statement":"The lesion localized to GSS; findings supported excess gamma-glutamylcysteine-derived 5-oxoproline production beyond disposal capacity.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"f388e4f8-2e86-5e2f-b588-a19f6f70c535","mechanism_event_label":"A blocked assembly pathway can also accumulate a side product.","subject":{"id":"60ab3ed3-3c4f-5728-8821-a311e71b264f","slug":"gss-deficient-patient-cells-1974","display_name":"GSS-deficient tissues from the two sisters studied in 1974","entity_type_key":"protein_state"},"object":{"id":"b6c43bfb-ad26-5060-ba07-6535c0f599c6","slug":"gss-deficiency-5-oxoprolinuria","display_name":"5-Oxoproline overproduction and urinary excretion in inherited GSS deficiency","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f388e4f8-2e86-5e2f-b588-a19f6f70c535","stable_key":"db0fc92e-b5ef-5667-a4c5-3ef257edbc9b:glutathione-gss-pyroglutamate-event","event_type":"biochemical_relationship","label":"A blocked assembly pathway can also accumulate a side product.","description":"The lesion localized to GSS; findings supported excess gamma-glutamylcysteine-derived 5-oxoproline production beyond disposal capacity.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d47d2006-2fb8-56ea-a76a-7919171f66ce","slug":"gamma-glutamylcysteine","display_name":"Gamma-glutamylcysteine","entity_type_key":"small_molecule"},"role":"upstream_intermediate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"46b7f404-3bf2-5bed-b4e2-f4c566fb5881","slug":"5-oxoproline","display_name":"L-5-Oxoproline / pyroglutamate","entity_type_key":"small_molecule"},"role":"accumulating_product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"60ab3ed3-3c4f-5728-8821-a311e71b264f","slug":"gss-deficient-patient-cells-1974","display_name":"GSS-deficient tissues from the two sisters studied in 1974","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b6c43bfb-ad26-5060-ba07-6535c0f599c6","slug":"gss-deficiency-5-oxoprolinuria","display_name":"5-Oxoproline overproduction and urinary excretion in inherited GSS deficiency","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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/glutathione-research/4152248.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5\", \"start_char\": 0, \"end_char\": 750, \"text_sha256\": \"67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Enzyme studies in two affected sisters","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Inherited 5-oxoprolinuria","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small historical disease study; overproduction mechanism is the authors’ interpretation, not a universal cause of acidosis.","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":"A blocked assembly pathway can also accumulate a side product.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[glutathione-p4152248] Glutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria). (1974). https://pubmed.ncbi.nlm.nih.gov/4152248/ DOI: 10.1073/pnas.71.6.2505","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Placenta, fibroblasts and erythrocytes","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":"8a0435bf-5182-53c3-bc75-2fdb3d782989","evidence_kind":"source_excerpt","locator":"Lines 437-448","start_line":437,"end_line":448,"excerpt":"### glutathione-gss-pyroglutamate\nThe lesion localized to GSS; findings supported excess gamma-glutamylcysteine-derived 5-oxoproline production beyond disposal capacity.\nCondition category: machinery_impairment\nnutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A blocked assembly pathway can also accumulate a side product.\norganism: Human\ntissue_or_cell_type: Placenta, fibroblasts and erythrocytes\nexperimental_model: Enzyme studies in two affected sisters\nlimitations: Small historical disease study; overproduction mechanism is the authors’ interpretation, not a universal cause of acidosis.\nexposure: Inherited 5-oxoprolinuria\nevidence_span: {\"source_cache\": \"artifacts/glutathione-research/4152248.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5\", \"start_char\": 0, \"end_char\": 750, \"text_sha256\": \"67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5\"}\n[glutathione-p4152248] Glutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria). 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