{"id":"edb19ea7-dc69-586d-a37e-588838a5d90c","stable_key":"0fa98914-9002-5798-9b64-48ec18430332:pea-receptor","predicate":"reported_relationship","statement":"Trace-amine receptor experiments support beta-phenylethylamine-responsive receptor signaling.","claim_class":"mechanistic","status":"source_recorded","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"4876775d-205a-59cb-a69d-107b296fba65","mechanism_event_label":"Trace-amine receptor experiments support beta-phenylethylamine-responsive receptor signaling.","subject":{"id":"ec05278e-4c90-596b-a263-7bc62d6c2245","slug":"beta-phenylethylamine","display_name":"Beta-Phenylethylamine / PEA","entity_type_key":"small_molecule"},"object":{"id":"02fff1f5-8333-5e83-a800-65c12d1622fd","slug":"taar1-assay","display_name":"TAAR1 receptor activation assay","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4876775d-205a-59cb-a69d-107b296fba65","stable_key":"0fa98914-9002-5798-9b64-48ec18430332:pea-receptor-event","event_type":"biochemical_relationship","label":"Trace-amine receptor experiments support beta-phenylethylamine-responsive receptor signaling.","description":"<!-- section:trace-and-d -->\nTrace-amine receptor cloning experiments showed activation/binding by biogenic amines including beta-phenylethylamine, supporting a receptor branch downstream of amino-acid decarboxylation. They do not demonstrate that oral Phe increases useful human brain signaling, that chocolate works through this route, or a universal half-life for PEA. MAO inhibition, tyramine exposure and Phe precursor supply are distinct conditions.\n\nIn a 1981 tracer report, one healthy woman received 8 mg/kg labeled D- or L-Phe. Labeled Tyr and protein-bound Phe appeared after either isomer; D-derived Phe appeared more prominently and cleared more slowly. This disproves absolute metabolic inertness of D-Phe but does not show that ribosomes directly incorporate D-Phe, identify a single human racemase, or establish equivalent nutrition across populations.\n\nA 30-person chronic-pain crossover trial comparing D-Phe 250 mg four times daily for four weeks with placebo did not show analgesic superiority. Proposed enkephalin preservation is not verified by that trial, and carboxypeptidase A is not neprilysin. A separate 20-person 150 mg/kg tyrosine study reported a selective working-memory benefit during multitasking with other task nulls; that is tyrosine evidence, not a phenylalanine efficacy trial.\n\nSources: [Trace amines: identification of a family of mammalian G protein-coupled receptors](https://pubmed.ncbi.nlm.nih.gov/11459929/); [Studies on phenylalanine metabolism by tracer techniques. IV. Biotransformation of D- and L-phenylalanine in man](https://pubmed.ncbi.nlm.nih.gov/7273250/); [Analgesic effectiveness of D-phenylalanine in chronic pain patients](https://pubmed.ncbi.nlm.nih.gov/3524509/); [Tyrosine improves working memory in a multitasking environment](https://pubmed.ncbi.nlm.nih.gov/10548261/)\n<!-- end:trace-and-d -->","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ec05278e-4c90-596b-a263-7bc62d6c2245","slug":"beta-phenylethylamine","display_name":"Beta-Phenylethylamine / PEA","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"as reported","sequence_order":0,"notes":""},{"entity":{"id":"02fff1f5-8333-5e83-a800-65c12d1622fd","slug":"taar1-assay","display_name":"TAAR1 receptor activation assay","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"not_reported","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary indexed abstract and bibliographic record; full experimental methods not independently extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cloned mammalian GPCR systems; primary abstract, exact species-specific potency not extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No inference of oral Phe brain benefit or chocolate effects.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Phenylalanine collection; chapter membership is not a causal effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-phenylalanine","display_name":"L-Phenylalanine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Trace-amine receptor experiments support beta-phenylethylamine-responsive receptor signaling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Trace amines: identification of a family of mammalian G protein-coupled receptors. | 2001 | DOI 10.1073/pnas.151105198 | PMID 11459929 | https://pubmed.ncbi.nlm.nih.gov/11459929/ | https://doi.org/10.1073/pnas.151105198","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 171-179; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"80f146ca-9efa-5623-ae26-5316c307b8a5","evidence_kind":"source_excerpt","locator":"Lines 171-179","start_line":171,"end_line":179,"excerpt":"<!-- section:trace-and-d -->\nTrace-amine receptor cloning experiments showed activation/binding by biogenic amines including beta-phenylethylamine, supporting a receptor branch downstream of amino-acid decarboxylation. They do not demonstrate that oral Phe increases useful human brain signaling, that chocolate works through this route, or a universal half-life for PEA. MAO inhibition, tyramine exposure and Phe precursor supply are distinct conditions.\n\nIn a 1981 tracer report, one healthy woman received 8 mg/kg labeled D- or L-Phe. Labeled Tyr and protein-bound Phe appeared after either isomer; D-derived Phe appeared more prominently and cleared more slowly. This disproves absolute metabolic inertness of D-Phe but does not show that ribosomes directly incorporate D-Phe, identify a single human racemase, or establish equivalent nutrition across populations.\n\nA 30-person chronic-pain crossover trial comparing D-Phe 250 mg four times daily for four weeks with placebo did not show analgesic superiority. Proposed enkephalin preservation is not verified by that trial, and carboxypeptidase A is not neprilysin. A separate 20-person 150 mg/kg tyrosine study reported a selective working-memory benefit during multitasking with other task nulls; that is tyrosine evidence, not a phenylalanine efficacy trial.\n\nSources: [Trace amines: identification of a family of mammalian G protein-coupled receptors](https://pubmed.ncbi.nlm.nih.gov/11459929/); [Studies on phenylalanine metabolism by tracer techniques. IV. Biotransformation of D- and L-phenylalanine in man](https://pubmed.ncbi.nlm.nih.gov/7273250/); [Analgesic effectiveness of D-phenylalanine in chronic pain patients](https://pubmed.ncbi.nlm.nih.gov/3524509/); [Tyrosine improves working memory in a multitasking environment](https://pubmed.ncbi.nlm.nih.gov/10548261/)\n<!-- end:trace-and-d -->","model_system":"Cloned mammalian GPCR systems; primary abstract, exact species-specific potency not extracted.","directness":"reported_statement","verification_status":"source_recorded","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"6cfe84b7-681c-5662-975c-76cd0bbfe9bd","stable_key":"import-0fa98914-9002-5798-9b64-48ec18430332","title":"L-Phenylalanine: detailed mechanisms of action (reviewed 5 October 2026)","document_type":"imported_text","citation_label":"Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication.","file_path":"","sha256":"8bd35f59dff5e70341a28440bbca3b35ba5cb5a6973c7a43b67c3ba9276a4048","revision_id":"2c907770-fbde-514b-9665-b847cfce9ca1","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}