title: First identification of a 2-ketoglutarate/isocitrate transport system in mammalian peroxisomes and its characterization.
abstract: Peroxisomes contain specific transporter proteins required for the translocation of various metabolites across its membrane. The presence of several members of the ATP-binding cassette (ABC) transporter family is well established, and the characterization of transporters for adenine nucleotides and (pyro)phosphate in the peroxisomal membrane has been described recently. Previously published data strongly suggest the presence of additional transporters that facilitate the translocation of reducing equivalents and acetyl-units across the peroxisomal membrane. In this paper, we demonstrate the presence of transporter activity for 2-ketoglutarate and isocitrate in the peroxisomal membrane, by functional reconstitution of bovine kidney peroxisomal membrane protein in proteoliposomes. This transporter activity is assumed to be required to sustain the activity of intraperoxisomal isocitrate-dehydrogenase, which is involved in the regeneration of NADPH in the peroxisomal matrix.
authors.affiliation: University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry and Pediatrics, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
authors.forename: Wouter F
authors.initials: WF
authors.lastname: Visser
authors.forename: Carlo W T
authors.initials: CW
authors.lastname: van Roermund
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Ijlst
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Hellingwerf
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002499:Centrifugation, Density Gradient; D029382:Dicarboxylic Acid Transporters / Q000302:isolation & purification / Q000378:metabolism*; D007523:Isocitrates / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism*; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D029382:Dicarboxylic Acid Transporters; D007523:Isocitrates; D007656:Ketoglutaric Acids; D011510:Proteolipids; C020485:proteoliposomes; C034219:isocitric acid