{"id":"91482982-98f9-5ead-b3c3-cc87eacd651e","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-spt-mutant-substrate","predicate":"favor_alanine_substrate","statement":"Human SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; amino-acid availability modulated this production.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"6a678b0f-bfcb-5818-b03d-e005b6205dcf","mechanism_event_label":"An enzyme can make different lipids when its substrate preference changes.","subject":{"id":"3e30b092-9f1c-5c77-9990-c845c33f6fa9","slug":"human-sptlc1-hsan1-variants","display_name":"Human HSAN1-associated SPTLC1 variants","entity_type_key":"cellular_process"},"object":{"id":"4d9df16d-24fa-5dc5-ab2a-2369a6a0399d","slug":"1-deoxysphingolipids","display_name":"1-Deoxysphingolipids","entity_type_key":"lipid"},"evidence_count":1,"mechanism_event":{"id":"6a678b0f-bfcb-5818-b03d-e005b6205dcf","stable_key":"10aa417f-4b03-599f-a453-4aa09edeb27c:alanine-spt-mutant-substrate-event","event_type":"observed_relationship","label":"An enzyme can make different lipids when its substrate preference changes.","description":"Human SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; 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unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human SPTLC1 variants expressed in HEK cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Variant-dependent abnormal chemistry is not a universal response to alanine intake.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"alanine","display_name":"L-Alanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"An enzyme can make different lipids when its substrate preference changes.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"3372c911-00d5-5dd9-9932-9eb13e222dc9","evidence_kind":"source_excerpt","locator":"Lines 424-430","start_line":424,"end_line":430,"excerpt":"## alanine-spt-mutant-substrate\nAn enzyme can make different lipids when its substrate preference changes.\nHuman SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; amino-acid availability modulated this production.\nModel: Human SPTLC1 variants expressed in HEK cells.\nLimitations: Variant-dependent abnormal chemistry is not a universal response to alanine intake.\nEvidence access: Primary abstract\nOral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549","model_system":"Human SPTLC1 variants expressed in HEK cells.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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