Functional characterization of 5-oxoproline transport via SLC16A1/MCT1

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 m 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.