Slc43a3, encoding equilibrative nucleobase transporter 1 (ENBT1), is an important solute carrier transporter. It functions as a purine-selective nucleobase transporter involved in purine salvage, facilitating the cellular uptake of extracellular purine nucleobases in cooperation with salvage enzymes [2]. It also plays a role in the transmembrane transport of various substances, which is crucial for the metabolism and functions of cells, and is associated with multiple biological processes and diseases [4].

In adipocytes, knockdown of Slc43a3 with siRNA reduced both basal and forskolin-stimulated FA efflux, increased FA uptake and lipid droplet accumulation, while its overexpression had the opposite effects, indicating it regulates free fatty acid (FA) flux, being a positive regulator of FA efflux and a negative regulator of FA uptake [1]. In mice, genetic deletion of slc43a3 dramatically reduced the absorption of 6-mercaptopurine (6-MP) from the gastrointestinal tract and attenuated its levels in peripheral tissues, suggesting that differences in SLC43A3 expression in humans may contribute to the variability in 6-MP plasma levels and therapeutic response [3].

In summary, Slc43a3 is a key transporter involved in purine salvage and the regulation of fatty acid flux. The use of gene knockout mouse models, like the slc43a3-deficient mice, has revealed its important role in drug absorption and distribution of 6-MP, and in the regulation of fatty acid metabolism in adipocytes, providing insights into relevant disease mechanisms and potential therapeutic targets.

References:

1. Hasbargen, Kathrin B, Shen, Wen-Jun, Zhang, Yiqiang, Azhar, Salman, Kraemer, Fredric B. 2020. Slc43a3 is a regulator of free fatty acid flux. In Journal of lipid research, 61, 734-745. doi:10.1194/jlr.RA119000294. https://pubmed.ncbi.nlm.nih.gov/32217606/

2. Furukawa, Junji, Inoue, Katsuhisa, Maeda, Junya, Matsuo, Hirotaka, Yuasa, Hiroaki. 2015. Functional identification of SLC43A3 as an equilibrative nucleobase transporter involved in purine salvage in mammals. In Scientific reports, 5, 15057. doi:10.1038/srep15057. https://pubmed.ncbi.nlm.nih.gov/26455426/

3. Sayler, Aaron L, Dean, Hannah, Hammond, James R. 2025. Impact of the loss of slc43a3 on 6-mercaptopurine absorption and tissue distribution in mice. In Drug metabolism and disposition: the biological fate of chemicals, 53, 100054. doi:10.1016/j.dmd.2025.100054. https://pubmed.ncbi.nlm.nih.gov/40133022/

4. Wu, Wenjie, Jiang, Cheng, Zhu, Wende, Jiang, Xiaobing. . Multi-omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma. In Journal of cellular and molecular medicine, 28, e18339. doi:10.1111/jcmm.18339. https://pubmed.ncbi.nlm.nih.gov/38687049/