title: Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine.
abstract: Nε-Trimethyllysine hydroxylase (TMLH) catalyses the first step in mammalian biosynthesis of carnitine, which plays a crucial role in fatty acid metabolism. The stereochemistry of the 3-hydroxy-Nε-trimethyllysine product of TMLH has not been defined. We report enzymatic and asymmetric synthetic studies, which define the product of TMLH catalysis as (2S,3S)-3-hydroxy-Nε-trimethyllysine.
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk.
authors.forename: Robert K
authors.identifier: http://orcid.org/0000-0002-8712-9901
authors.initials: RK
authors.lastname: Leśniak
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk.
authors.forename: Suzana
authors.initials: S
authors.lastname: Markolovic
authors.affiliation: Biomedical Research and Study Centre, Ratsupites 1, LV1067 Riga, Latvia.
authors.forename: Kaspars
authors.initials: K
authors.lastname: Tars
authors.affiliation: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk.
authors.forename: Christopher J
authors.identifier: http://orcid.org/0000-0002-0290-6565
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: D055162:Biocatalysis; D002331:Carnitine / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: C003712:trimethyllysine; D006899:Mixed Function Oxygenases; C025931:trimethyl-lysine hydroxylase; D008239:Lysine; D002331:Carnitine