The mitochondrial ornithine transporter: Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms

Giuseppe Fiermonte, Vincenza Dolce, Laura David, Filippo Maria Santorelli, Carlo Dionisi-Vici, Ferdinando Palmieri, John E. Walker

Research output: Contribution to journalArticlepeer-review

Abstract

Two isoforms of the human ornithine carrier, ORC1 and ORC2, have been identified by overexpression of the proteins in bacteria and by study of the transport properties of the purified proteins reconstituted into liposomes. Both transport L-isomers of ornithine, lysine, arginine, and citrulline by exchange and by unidirectional mechanisms, and they are inactivated by the same inhibitors. ORC2 has a broader specificity than ORC1, and L- and D-histidine, L-homoarginine, and D-isomers of ornithine, lysine, and ornithine are all substrates. Both proteins are expressed in a wide range of human tissues, but ORC1 is the predominant form. The highest levels of expression of both isoforms are in the liver. Five mutant forms of ORC1 associated with the human disease hyperornithinemia-hyperammonemia-homocitrullinuria were also made. The mutations abolish the transport properties of the protein. In patients with hyperornithinemia-hyperammonemia-homocitrullinuria, isoform ORC2 is unmodified, and its presence compensates partially for defective ORC1.

Original languageEnglish
Pages (from-to)32778-32783
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number35
DOIs
Publication statusPublished - Aug 29 2003

ASJC Scopus subject areas

  • Biochemistry

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