{"id":"39b8551c-498c-5906-9251-730fef90df1b","stable_key":"104835a3-b891-5dc4-a6bb-42ab7c6f96c4:butyrate-phd2-inhibition","predicate":"inhibits","statement":"Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e2168f86-db4b-5534-9a6e-b3228ffa0f14","mechanism_event_label":"It also directly affected an enzyme that normally marks HIF for degradation.","subject":{"id":"e7428a7f-d35a-5406-9904-a88984814833","slug":"butyrate","display_name":"Butyrate","entity_type_key":"small_molecule"},"object":{"id":"8681acd7-4f56-59e0-a757-37b8376c8bde","slug":"egln1","display_name":"EGLN1 / PHD2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"e2168f86-db4b-5534-9a6e-b3228ffa0f14","stable_key":"104835a3-b891-5dc4-a6bb-42ab7c6f96c4:butyrate-phd2-inhibition-event","event_type":"observed_relationship","label":"It also directly affected an enzyme that normally marks HIF for degradation.","description":"Butyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e7428a7f-d35a-5406-9904-a88984814833","slug":"butyrate","display_name":"Butyrate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8681acd7-4f56-59e0-a757-37b8376c8bde","slug":"egln1","display_name":"EGLN1 / PHD2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"628ddc2d-e4d9-59c7-ae76-0c0cab80a6b1","slug":"2-oxoglutarate","display_name":"2-Oxoglutarate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"38d0c4d9-53d1-5239-bfe3-c1b5e9b79085","slug":"ascorbate","display_name":"L-Ascorbate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"22b3e241-94b0-55fd-a233-c63af92520d8","slug":"hif1a","display_name":"HIF-1 alpha","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text, recombinant methods and enzyme kinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human PHD2 residues 181–402; NMR and enzymatic assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"butyrate","display_name":"Butyrate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"It also directly affected an enzyme that normally marks HIF for degradation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ba6658d8-9de1-56ca-afbd-6b619b385338","evidence_kind":"source_excerpt","locator":"Lines 246-252","start_line":246,"end_line":252,"excerpt":"## butyrate-phd2-inhibition\nIt also directly affected an enzyme that normally marks HIF for degradation.\nButyrate bound and inhibited a recombinant human PHD2 catalytic fragment; kinetic analysis gave a noncompetitive Ki of 5.3 ± 0.5 mM relative to 2-oxoglutarate.\nModel: Human PHD2 residues 181–402; NMR and enzymatic assays.\nLimitations: Millimolar assay exposure is relevant to local gut questions, not evidence of inhibition throughout the body at normal blood levels.\nEvidence access: Primary full text, recombinant methods and enzyme kinetics\nMicrobiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34190032/ · DOI 10.1080/19490976.2021.1938380","model_system":"Human PHD2 residues 181–402; NMR and enzymatic assays.","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":"33205bb8-dcbe-5d2c-afca-86075d7748d1","stable_key":"import-104835a3-b891-5dc4-a6bb-42ab7c6f96c4","title":"Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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