{"id":"733d5047-ba07-5fb8-8d83-c4c9392f6f2e","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-diet-erythropoiesis","predicate":"supports","statement":"Histidine-deficient feeding lowered hematocrit by 25 +/- 9 percent while serum iron rose; repletion produced reticulocytosis, higher hematocrit and a fall in serum iron.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3a87f444-dd4a-5fda-9eb9-214fcc01247e","mechanism_event_label":"Red-cell production failed despite more iron in serum.","subject":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"object":{"id":"534a4d9a-691d-5944-871f-ad76d4e7bfd2","slug":"human-histidine-erythropoiesis","display_name":"Erythropoiesis during controlled histidine depletion","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3a87f444-dd4a-5fda-9eb9-214fcc01247e","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-diet-erythropoiesis-event","event_type":"observed_relationship","label":"Red-cell production failed despite more iron in serum.","description":"Histidine-deficient feeding lowered hematocrit by 25 +/- 9 percent while serum iron rose; repletion produced reticulocytosis, higher hematocrit and a fall in serum iron.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"534a4d9a-691d-5944-871f-ad76d4e7bfd2","slug":"human-histidine-erythropoiesis","display_name":"Erythropoiesis during controlled histidine depletion","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Controlled sequential metabolic-unit feeding in four healthy and three chronically uremic men; histidine-deficient amino-acid diet for 35 +/- 2 days, followed by histidine-containing diet for 31 +/- 5 days.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small historical nonrandomized sequential study; mixed renal status and artificial diet. Does not define a universal plasma cutoff, ordinary dietary prevalence or replacement dose. Changes do not identify the exact iron-handling mechanism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Red-cell production failed despite more iron in serum.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Evidence that histidine is an essential amino acid in normal and chronically uremic man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1123426/ · DOI 10.1172/JCI108016","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"78918b6e-f8d0-5312-af58-c107466245a7","evidence_kind":"source_excerpt","locator":"Lines 42-48","start_line":42,"end_line":48,"excerpt":"## histidine-diet-erythropoiesis\nRed-cell production failed despite more iron in serum.\nHistidine-deficient feeding lowered hematocrit by 25 +/- 9 percent while serum iron rose; repletion produced reticulocytosis, higher hematocrit and a fall in serum iron.\nModel: Controlled sequential metabolic-unit feeding in four healthy and three chronically uremic men; histidine-deficient amino-acid diet for 35 +/- 2 days, followed by histidine-containing diet for 31 +/- 5 days.\nLimitations: Small historical nonrandomized sequential study; mixed renal status and artificial diet. Does not define a universal plasma cutoff, ordinary dietary prevalence or replacement dose. Changes do not identify the exact iron-handling mechanism.\nEvidence access: Primary abstract\nEvidence that histidine is an essential amino acid in normal and chronically uremic man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1123426/ · DOI 10.1172/JCI108016","model_system":"Controlled sequential metabolic-unit feeding in four healthy and three chronically uremic men; histidine-deficient amino-acid diet for 35 +/- 2 days, followed by histidine-containing diet for 31 +/- 5 days.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}