title: γ-Butyrobetaine hydroxylase catalyses a Stevens type rearrangement.
abstract: γ-Butyrobetaine hydroxylase (BBOX) is a 2-oxoglutarate and Fe(II)-dependent oxygenase that catalyses the final step of L-carnitine biosynthesis in animals. BBOX catalyses the oxidation of 3-(2,2,2-trimethylhydrazinium)propionate (THP), a clinically used BBOX inhibitor, to form multiple products including 3-amino-4-(methyamino)butanoic acid (AMBA), which is proposed to be formed via a Stevens type rearrangement mechanism. We report the synthesis of AMBA and confirm that it is a product of the BBOX catalysed oxidation of THP. AMBA reacts with formaldehyde, which is produced enzymatically by BBOX, to give a cyclic adduct.
authors: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Oxford, United Kingdom.
authors: Luc
authors: L
authors: Henry
authors: Ivanhoe K H
authors: IK
authors: Leung
authors: Timothy D W
authors: TD
authors: Claridge
authors: Christopher J
authors: CJ
authors: Schofield
mesh_terms: D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D008744:Methylamines / Q000138:chemical synthesis / Q000737:chemistry*; D008763:Methylhydrazines / Q000138:chemical synthesis / Q000737:chemistry*; D010084:Oxidation-Reduction; D050563:gamma-Butyrobetaine Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C576336:3-amino-4-(methyamino)butanoic acid; D002087:Butyrates; D004791:Enzyme Inhibitors; D008744:Methylamines; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D050563:gamma-Butyrobetaine Dioxygenase