title: Functional characterization of 5-oxoproline transport via SLC16A1/MCT1.
abstract: Thyrotropin-releasing hormone is a tripeptide that consists of 5-oxoproline, histidine, and proline. The peptide is rapidly metabolized by various enzymes. 5-Oxoproline is produced by enzymatic hydrolysis in a variety of peptides. Previous studies showed that 5-oxoproline could become a possible biomarker for autism spectrum disorders. Here we demonstrate the involvement of SLC16A1 in the transport of 5-oxoproline. An SLC16A1 polymorphism (rs1049434) was recently identified. However, there is no information about the effect of the polymorphism on SLC16A1 function. In this study, the polymorphism caused an observable change in 5-oxoproline and lactate transport via SLC16A1. The Michaelis constant (Km) was increased in an SLC16A1 mutant compared with that in the wild type. In addition, the proton concentration required to produce half-maximal activation of transport activity (K0.5, H (+)) was increased in the SLC16A1 mutant compared with that in the wild type. Furthermore, we examined the transport of 5-oxoproline in T98G cells as an astrocyte cell model. Despite the fact that 5-oxoproline is an amino acid derivative, Na(+)-dependent and amino acid transport systems scarcely contributed to 5-oxoproline transport. Based on our findings, we conclude that H(+)-coupled 5-oxoproline transport is mediated solely by SLC16A1 in the cells.
authors.affiliation: From the Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812 and.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: From the Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812 and.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Futagi
authors.affiliation: From the Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812 and.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: From the Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812 and.
authors.forename: Jiro
authors.initials: J
authors.lastname: Ogura
authors.affiliation: From the Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812 and the Department of Pharmacy, Hokkaido University Hospital, Sapporo 060-8648, Japan ken-i@pharm.hokudai.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D014644:Genetic Variation; D006801:Humans; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009865:Oocytes; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011522:Protons; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D014982:Xenopus laevis; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D027501:Monocarboxylic Acid Transporters; D011522:Protons; D011761:Pyrrolidonecarboxylic Acid; D012333:RNA, Messenger; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1
keywords: Brain; Proton Transport; Single-nucleotide Polymorphism (SNP); Transporter; Xenopus