RRC ID 68087
Author Sasaki S, Futagi Y, Kobayashi M, Ogura J, Iseki K.
Title Functional characterization of 5-oxoproline transport via SLC16A1/MCT1.
Journal J Biol Chem
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.
Volume 290(4)
Pages 2303-11
Published 2015-1-23
DOI 10.1074/jbc.M114.581892
PII S0021-9258(20)57768-5
PMID 25371203
PMC PMC4303682
MeSH Animals Astrocytes / metabolism* Biological Transport Brain / metabolism* Catalytic Domain Cell Line, Tumor Genetic Variation Humans Monocarboxylic Acid Transporters / metabolism* Mutagenesis, Site-Directed Mutation, Missense Oocytes Polymorphism, Genetic Polymorphism, Single Nucleotide Protons Pyrrolidonecarboxylic Acid / metabolism* RNA, Messenger / metabolism Symporters / metabolism* Xenopus laevis
IF 4.238
Human and Animal Cells T98G(RCB1954)