{"id":"b128d239-66cf-5fad-bc6c-3b5d4ce2172d","stable_key":"3b5aff9b-4086-5574-bfb4-3ea49ba520d7:coq10-hma-headgroup","predicate":"is_intermediate_in","statement":"Isotope tracing identified 4-hydroxymandelate as a CoQ10 head-group biosynthetic intermediate.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"007a36af-ce4f-5fb8-836e-8406c9b8fc90","mechanism_event_label":"The head group has its own supply route, separate from the lipid tail.","subject":{"id":"4d1110c4-dcaf-5522-9f71-a8c2c16cd62d","slug":"4-hydroxymandelate","display_name":"4-Hydroxymandelate / 4-HMA","entity_type_key":"small_molecule"},"object":{"id":"284bedca-d50b-5a10-a431-3082bcfe68de","slug":"coq-headgroup-biosynthesis","display_name":"Coenzyme Q aromatic head-group biosynthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"007a36af-ce4f-5fb8-836e-8406c9b8fc90","stable_key":"3b5aff9b-4086-5574-bfb4-3ea49ba520d7:coq10-hma-headgroup-event","event_type":"biochemical_relationship","label":"The head group has its own supply route, separate from the lipid tail.","description":"Isotope tracing identified 4-hydroxymandelate as a CoQ10 head-group biosynthetic intermediate.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"bcfef85f-831d-5439-ba51-1aef4b090441","slug":"l-tyrosine","display_name":"L-Tyrosine","entity_type_key":"small_molecule"},"role":"upstream_precursor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4d1110c4-dcaf-5522-9f71-a8c2c16cd62d","slug":"4-hydroxymandelate","display_name":"4-Hydroxymandelate / 4-HMA","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"284bedca-d50b-5a10-a431-3082bcfe68de","slug":"coq-headgroup-biosynthesis","display_name":"Coenzyme Q aromatic head-group biosynthesis","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/coq10-research/34471290.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956\", \"start_char\": 0, \"end_char\": 1028, \"text_sha256\": \"a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Oxygen-isotope metabolomics and enzyme perturbation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"18O2 labeling and HPDL activity","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cellular pathway; no evidence that additional tyrosine treats every CoQ deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"coq10","display_name":"Coenzyme Q10 / CoQ10 redox system","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human cell lines","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The head group has its own supply route, separate from the lipid tail.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[coq10-p34471290] The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/34471290/ DOI: 10.1038/s41586-021-03865-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Tyrosine-derived CoQ head-group precursor","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8689132c-e39c-5b43-b15e-5e4ab30b2aca","evidence_kind":"source_excerpt","locator":"Lines 177-188","start_line":177,"end_line":188,"excerpt":"### coq10-hma-headgroup\nIsotope tracing identified 4-hydroxymandelate as a CoQ10 head-group biosynthetic intermediate.\nCondition category: normal\nnutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The head group has its own supply route, separate from the lipid tail.\norganism: Human cell lines\ntissue_or_cell_type: Tyrosine-derived CoQ head-group precursor\nexperimental_model: Oxygen-isotope metabolomics and enzyme perturbation\nlimitations: Cellular pathway; no evidence that additional tyrosine treats every CoQ deficiency.\nexposure: 18O2 labeling and HPDL activity\nevidence_span: {\"source_cache\": \"artifacts/coq10-research/34471290.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956\", \"start_char\": 0, \"end_char\": 1028, \"text_sha256\": \"a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956\"}\n[coq10-p34471290] The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. 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