open access

https://hdl.handle.net/2115/59282

Functional Characterization of 5-Oxoproline Transport via SLC16A1/MCT1

英語

single-nucleotide polymorphism

2015-01-23

American Society for Biochemistry and Molecular Biology

Journal of Biological Chemistry

290(4)

2303-2311

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 (K-m) 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 (K-0.5, 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.

学術雑誌論文

Accepted Manuscript

This research was originally published in Journal of Biological Chemistry. Shotaro Sasaki, Yuya Futagi, Masaki Kobayashi, Jiro Ogura, and Ken Iseki. Functional Characterization of 5-Oxoproline Transport via SLC16A1/MCT1. Journal of Biological Chemistry. 2015; 290(4):2303-2311. © the American Society for Biochemistry and Molecular Biology.

0021-9258