title: Submitochondrial localization of 6-N-trimethyllysine dioxygenase - implications for carnitine biosynthesis.
abstract: The first enzyme of carnitine biosynthesis is the mitochondrial 6-N-trimethyllysine 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-trimethyllysine transporter system. This transport system represents an additional step in carnitine biosynthesis that could have considerable implications for the regulation of carnitine biosynthesis.
authors.affiliation: Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Naomi
authors.initials: N
authors.lastname: van Vlies
authors.forename: Rob
authors.initials: R
authors.lastname: Ofman
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
mesh_terms: D000818:Animals; D002331:Carnitine / Q000096:biosynthesis*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000201:enzymology*
chemical_list: D006899:Mixed Function Oxygenases; C436318:epsilon-N-trimethyllysine hydroxylase; D002331:Carnitine