{"id":"42b43b61-4f3b-599f-aedb-77e196be35e6","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:tmlhe-hydroxylation","predicate":"converted_to","statement":"Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"699ec45f-6a95-5e9f-8b54-6983fb458c11","mechanism_event_label":"TMLHE begins conversion of released trimethyllysine toward carnitine.","subject":{"id":"6ded5960-aad7-562a-95a1-ee6ad138d19e","slug":"trimethyllysine","display_name":"Free N-epsilon-trimethyl-L-lysine","entity_type_key":"small_molecule"},"object":{"id":"30b9ea41-2d8d-58c7-8dfd-7307505f4576","slug":"hydroxytrimethyllysine","display_name":"(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"699ec45f-6a95-5e9f-8b54-6983fb458c11","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:tmlhe-hydroxylation-event","event_type":"biochemical_relationship","label":"TMLHE begins conversion of released trimethyllysine toward carnitine.","description":"Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3f888cec-e779-5b46-bd59-e5317d4bf6aa","slug":"tmlhe","display_name":"Trimethyllysine hydroxylase / TMLHE","entity_type_key":"protein"},"role":"catalyst","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6ded5960-aad7-562a-95a1-ee6ad138d19e","slug":"trimethyllysine","display_name":"Free N-epsilon-trimethyl-L-lysine","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"628ddc2d-e4d9-59c7-ae76-0c0cab80a6b1","slug":"2-oxoglutarate","display_name":"2-Oxoglutarate","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"899c7ab0-6f81-5b38-a6bd-fbb33d66ac8d","slug":"oxygen","display_name":"Molecular oxygen","entity_type_key":"small_molecule"},"role":"cosubstrate","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"cofactor","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"30b9ea41-2d8d-58c7-8dfd-7307505f4576","slug":"hydroxytrimethyllysine","display_name":"(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"462f63ce-a2c1-5312-9c14-70b8b12e1d6e","slug":"succinate","display_name":"Succinate","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"966f14e5-c82f-5535-ad89-bfcc0adb2232","slug":"carbon-dioxide","display_name":"Carbon dioxide","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"TMLHE begins conversion of released trimethyllysine toward carnitine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A\n[tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondrial carnitine-biosynthesis step","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"740968dd-ad0f-5aea-9a8b-149f24198a6f","evidence_kind":"source_excerpt","locator":"Lines 166-175","start_line":166,"end_line":175,"excerpt":"### tmlhe-hydroxylation\nHuman TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.\nPlain language: TMLHE begins conversion of released trimethyllysine toward carnitine.\nCondition category: normal\norganism: Homo sapiens\ntissue_or_cell_type: Mitochondrial carnitine-biosynthesis step\nexperimental_model: Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays\nlimitations: The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.\n[lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A\n[tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A","model_system":"Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact quote from the accompanying curation document, not from publisher text. Original study references: [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A; [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"7633bde7-dcc9-5086-91c6-a45eb96857f3","stable_key":"import-c3df3634-4c3a-5099-a5d9-e4f6344c1084","title":"L-Lysine: mechanism-first literature curation (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":"93998d47c21525409ba82f1c82ededf2893dff15fbe61c7deffc175b0e298e97","revision_id":"3897e31f-6624-59e1-a053-8a81b7361632","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}