{"id":"6098b8f9-8a50-5730-b6bb-9c8e2c3ff54d","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-proteolysis-affinity","predicate":"reduces","statement":"Pancreatic protease incubation at pH 8 partially degraded human R protein and lowered its cobalamin affinity approximately 150-fold.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"0c26542a-6002-5885-be61-4da1c3eec3db","mechanism_event_label":"Digestive proteases loosened haptocorrin binding.","subject":{"id":"72b9ea38-64f8-5d31-9850-94c27cc236ac","slug":"pancreatic-serine-proteases","display_name":"Pancreatic serine protease family","entity_type_key":"protein_family"},"object":{"id":"b0aa675b-7f86-5784-b281-c8c532cc5e61","slug":"haptocorrin-cobalamin-affinity","display_name":"Human haptocorrin affinity for cobalamin","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0c26542a-6002-5885-be61-4da1c3eec3db","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-abs-proteolysis-affinity-event","event_type":"biochemical_relationship","label":"Digestive proteases loosened haptocorrin binding.","description":"Pancreatic protease incubation at pH 8 partially degraded human R protein and lowered its cobalamin affinity approximately 150-fold.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"21f01bdf-1da9-59c3-af35-c67281e89dd4","slug":"tcn1","display_name":"Human haptocorrin / TCN1","entity_type_key":"protein"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"72b9ea38-64f8-5d31-9850-94c27cc236ac","slug":"pancreatic-serine-proteases","display_name":"Pancreatic serine protease family","entity_type_key":"protein_family"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b0aa675b-7f86-5784-b281-c8c532cc5e61","slug":"haptocorrin-cobalamin-affinity","display_name":"Human haptocorrin affinity for cobalamin","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human salivary R protein and gastric intrinsic factor in vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Pancreatic proteases at pH 8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Reconstituted binding/protease conditions; measured competition does not quantify absorption in an intact person. Individual protease isoforms and reagent species not resolved in abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Digestive proteases loosened haptocorrin binding.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[allen-1978-proteases] Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. (1978). https://pubmed.ncbi.nlm.nih.gov/22556/ DOI: 10.1172/jci108924","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Duodenal luminal model","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"fa89ca75-5635-5517-b213-143bd9540911","evidence_kind":"source_excerpt","locator":"Lines 166-177","start_line":166,"end_line":177,"excerpt":"### b12-abs-proteolysis-affinity\nPancreatic protease incubation at pH 8 partially degraded human R protein and lowered its cobalamin affinity approximately 150-fold.\nCondition category: normal\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Digestive proteases loosened haptocorrin binding.\norganism: Homo sapiens\ntissue_or_cell_type: Duodenal luminal model\nexperimental_model: Purified human salivary R protein and gastric intrinsic factor in vitro\nlimitations: Reconstituted binding/protease conditions; measured competition does not quantify absorption in an intact person. Individual protease isoforms and reagent species not resolved in abstract.\nexposure: Pancreatic proteases at pH 8\ncross_nutrient: false\n[allen-1978-proteases] Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. (1978). https://pubmed.ncbi.nlm.nih.gov/22556/ DOI: 10.1172/jci108924","model_system":"Purified human salivary R protein and gastric intrinsic factor in vitro","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [allen-1978-proteases] Effect of proteolytic enzymes on the binding of cobalamin to R protein and intrinsic factor. In vitro evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency. (1978). https://pubmed.ncbi.nlm.nih.gov/22556/ DOI: 10.1172/jci108924","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: mechanisms, 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":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}