tailieunhanh - Báo cáo khoa học: Submitochondrial localization of 6-N-trimethyllysine dioxygenase ) implications for carnitine biosynthesis

The first enzyme of carnitine biosynthesis is the mitochondrial 6-N-tri-methyllysine dioxygenase, which converts 6-N-trimethyllysine to 3-hydroxy-6-N-trimethyllysine. Using progressive membrane solubilization with digitonin and protease protection experiments, we show that this enzyme is localized in the mitochondrial matrix. | ỊFEBS Journal Submitochondrial localization of 6-N-trimethyllysine dioxygenase - implications for carnitine biosynthesis Naomi van Vlies Rob Ofman Ronald J. A. Wanders and Frederic M. Vaz Departments of ClinicalChemistry and Pediatrics Academic MedicalCenter University of Amsterdam the Netherlands Keywords carnitine biosynthesis HTML mitochondria TML TMLD Correspondence F. M. Vaz University of Amsterdam Academic Medical Center Departments of Clinical Chemistry and Pediatrics Laboratory Genetic Metabolic Diseases F0-224 PO Box 22700 1100 DE Amsterdam the Netherlands Fax 31 20 6962596 Tel 31 20 5665958 E-mail Received 16 June 2007 revised 9 September 2007 accepted 14 September 2007 The first enzyme of carnitine biosynthesis is the mitochondrial 6-N-tri-methyllysine dioxygenase which converts 6-N-trimethyllysine to 3-hydroxy-6-N-trimethyllysine. Using progressive membrane solubilization with digitonin and protease protection experiments we show that this enzyme is localized in the mitochondrial matrix. Latency experiments with intact mitochondria showed that 3-hydroxy-6-N-trimethyllysine formation is limited by 6-N-trimethyllysine transport across the mitochondrial inner membrane. Because the subsequent carnitine biosynthesis enzymes are cytosolic after production 3-hydroxy-6-N-trimethyllysine must be transported out of the mitochondria by a putative mitochondrial 6-N-trimethyllysine 3-hydroxy-6-N-trimethyl-lysine transporter system. This transport system represents an additional step in carnitine biosynthesis that could have considerable implications for the regulation of carnitine biosynthesis. doi Carnitine 3-hydroxy-4-N-trimethylaminobutyrate is a vital compound in fatty acid metabolism as it enables the transport of activated long-chain fatty acids and peroxisomal b-oxidation products into the mitochondrial matrix where b-oxidation takes place 1 2 . Mammals acquire carnitine both from their diet and through .