Advanced Science Research Center, Okayama University, Okayama 700-8530, Japan.
Curr Mol Pharmacol. 2013 Jul;6(2):88-94. doi: 10.2174/18744672113069990035.
SLC17A1 protein (NPT1) was the first identified member of the SLC17 phosphate transporter family, and is known to mediate Na(+)/inorganic phosphate (Pi) co-transport when expressed in Xenopus oocytes. Although this protein was suggested to be a renal polyspecific anion exporter, its transport properties were not well characterized. The clean biochemical approach revealed that proteoliposomes comprising purified NPT1 as the only protein source transport various organic anions such as urate, p-aminohippuric acid (PAH), and acetylsalicylic acid (aspirin) in a membrane potential (Δψ)-driven and Cl(-) -dependent manner. Human NPT1 carrying an SNP mutation, Thr269Ile, known to increase the risk of gout, exhibited 32% lower urate transport activity compared to the wild type protein, leading to the conclusion that NPT1 is the long searched for transporter responsible for renal urate excretion. In the present article, we summarized the history of identification of the urate exporter and its possible involvement in the dynamism of urate under physiological and pathological conditions.
SLC17A1 蛋白(NPT1)是第一个被鉴定的 SLC17 磷酸转运蛋白家族成员,当在非洲爪蟾卵母细胞中表达时,已知其介导 Na(+)/无机磷酸盐 (Pi) 共转运。尽管该蛋白被认为是一种肾脏多特异性阴离子外排体,但它的转运特性尚未得到很好的表征。通过清洁的生化方法发现,由纯化的 NPT1 作为唯一蛋白质来源组成的脂质体以膜电位 (Δψ) 驱动和 Cl(-) 依赖性方式转运各种有机阴离子,如尿酸、对氨基马尿酸 (PAH) 和乙酰水杨酸 (阿司匹林)。携带已知会增加痛风风险的 SNP 突变 Thr269Ile 的人 NPT1 与野生型蛋白相比,尿酸转运活性降低了 32%,这表明 NPT1 是长期寻找的负责肾脏尿酸排泄的转运体。在本文中,我们总结了尿酸外排体的鉴定历史及其在生理和病理条件下尿酸动态变化中的可能作用。