{"id":"067da1de-efad-52b0-bce8-8d95bbfd8e1a","stable_key":"649e861b-265a-5912-bc36-3a73e53ef892:l-serine-spt-low-serine-switch","predicate":"when_limited_changes","statement":"Limiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7582623f-de8e-5735-a59e-c66827866494","mechanism_event_label":"Restricting substrate can trade one abnormal lipid pattern for another.","subject":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"},"object":{"id":"924dae90-b9c9-5d11-a222-6b58f3936031","slug":"human-sptlc1-als-lipid-substrate-switch","display_name":"Substrate-dependent lipid signature in human SPTLC1-ALS models","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7582623f-de8e-5735-a59e-c66827866494","stable_key":"649e861b-265a-5912-bc36-3a73e53ef892:l-serine-spt-low-serine-switch-event","event_type":"observed_relationship","label":"Restricting substrate can trade one abnormal lipid pattern for another.","description":"Limiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c882cd0b-9d83-5b07-bd1c-fe4d45657dcb","slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"924dae90-b9c9-5d11-a222-6b58f3936031","slug":"human-sptlc1-als-lipid-substrate-switch","display_name":"Substrate-dependent lipid signature in human SPTLC1-ALS models","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4d9df16d-24fa-5dc5-ab2a-2369a6a0399d","slug":"1-deoxysphingolipids","display_name":"1-Deoxysphingolipids","entity_type_key":"lipid"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"da1ba1a7-e457-5459-8e95-a2c405c3330c","slug":"sptlc1","display_name":"Human serine palmitoyltransferase long-chain base subunit 1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"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":"Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Neither unrestricted supplementation nor restriction is shown to be a universal remedy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-serine","display_name":"L-Serine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Restricting substrate can trade one abnormal lipid pattern for another.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35900868/ · DOI 10.1172/JCI161908","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":"d9db3027-6d7c-5420-a63d-62cdf7ad1ba7","evidence_kind":"source_excerpt","locator":"Lines 326-332","start_line":326,"end_line":332,"excerpt":"## l-serine-spt-low-serine-switch\nRestricting substrate can trade one abnormal lipid pattern for another.\nLimiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature.\nModel: Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context.\nLimitations: Neither unrestricted supplementation nor restriction is shown to be a universal remedy.\nEvidence access: Primary abstract\nSPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35900868/ · DOI 10.1172/JCI161908","model_system":"Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context.","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":"70bcf57a-36bb-563f-9073-2d616e5f155a","stable_key":"import-649e861b-265a-5912-bc36-3a73e53ef892","title":"L-Serine: synthesis, one-carbon metabolism, lipids 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":"22a750ce2b94f8607268c58322c48c4f0468f403b72a4008307538a6e5ff86d5","revision_id":"c1d6a7e1-9558-5bc6-9e3b-7080c26d3dbc","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}