γ-Butyrobetaine hydroxylase catalyses a Stevens type rearrangement

Journal article

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. © 2012 Elsevier Ltd. All rights reserved.

Authors: Henry, L; Leung, I; Claridge, T; Schofield, C

• Journal: Bioorganic and Medicinal Chemistry Letters
• Volume: 22
• Issue: 15
• Pages: 4975-4978
• Publication date: 2012-08-01
• DOI: 10.1016/j.bmcl.2012.06.024
• EISSN: 1464-3405
• ISSN: 0960-894X
• Language: English
• Keywords: 2-Oxoglutarate (2OG) oxygenase; BBOX; Trimethyl l-lysine; Fatty acid oxidation; Carnitine; THP; Stevens rearrangement; Formaldehyde