{"id":"c86e30e1-bd26-529a-b6ac-58d92b1519c6","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-spt-ormdl-gating","predicate":"inhibits","statement":"ORMDL3 restricts access to the substrate tunnel of the PLP-dependent human SPT complex.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"fb4d7b13-ccb2-5eaa-940f-b12b796b801a","mechanism_event_label":"Cofactor availability is only one control on sphingolipid production.","subject":{"id":"ad79f5dc-2ce9-5345-ab76-3078af34148f","slug":"ormdl3","display_name":"Human ORMDL sphingolipid biosynthesis regulator 3","entity_type_key":"protein"},"object":{"id":"25fd8f94-278f-5967-ba2c-37debeae2e65","slug":"human-serine-palmitoyltransferase-complex","display_name":"Human SPTLC1-SPTLC2-SPTSSA complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"fb4d7b13-ccb2-5eaa-940f-b12b796b801a","stable_key":"1310afbd-6010-586e-805d-551d846da421:b6-neuro-spt-ormdl-gating-event","event_type":"biochemical_relationship","label":"Cofactor availability is only one control on sphingolipid production.","description":"ORMDL3 restricts access to the substrate tunnel of the PLP-dependent human SPT complex.","status":"provisional","compartment":{"slug":"endoplasmic-reticulum","display_name":"Endoplasmic reticulum"},"participants":[{"entity":{"id":"ad79f5dc-2ce9-5345-ab76-3078af34148f","slug":"ormdl3","display_name":"Human ORMDL sphingolipid biosynthesis regulator 3","entity_type_key":"protein"},"role":"regulator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"25fd8f94-278f-5967-ba2c-37debeae2e65","slug":"human-serine-palmitoyltransferase-complex","display_name":"Human SPTLC1-SPTLC2-SPTSSA complex","entity_type_key":"protein_complex"},"role":"enzyme-complex","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"cofactor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Recombinant complex structures and functional assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Ceramide sensing was proposed; these structures alone do not establish its complete mechanism.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b6","display_name":"Vitamin B6","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Cofactor availability is only one control on sphingolipid production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified recombinant protein; 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Study references: [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"251773bb-16f5-5903-b135-db4a61d9dec4","stable_key":"import-1310afbd-6010-586e-805d-551d846da421","title":"Vitamin B6: 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":"ef0019b344b2219220f801a84d0d138ff6880c1be1a59540d9034bfa4334f61e","revision_id":"cac3555f-48af-5c52-a84e-add4482c87fb","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}