Human urate transporter 1 (hURAT1) mediates the transport of orotate
Human urate transporter 1 (hURAT1) mediates the transport of orotate
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DOI：
10.1007/s12576-011-0136-0
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发表时间：
2011-05-01
影响因子：
2.3
通讯作者：
Endou, Hitoshi
中科院分区：
文献类型：
--
作者：
Miura, Daisaku;Anzai, Naohiko;Endou, Hitoshi
旋酸酯是合成嘧啶的前体。肾脏使用外源性旋酸酯合成尿苷二磷酸糖，尿苷二磷酸糖用于肾小球和肾小管基底膜中胶原蛋白的糖基化。Orotate摄取发生在肝脏和肾脏，但其分子机制在很大程度上是未知的。由于在刷状膜泡研究中，orotate已被证明是肾尿酸盐/阴离子交换剂的底物，我们使用表达hURAT1 （HEK-hURAT1）的HEK293细胞研究了人类URAT1 （hURAT1）是否介导了orotate的转运。hURAT1介导的羊角酸盐摄取具有时间和剂量依赖性（K(m) 5.2 μ m）。hURAT1介导的[(3)H]羊角酸盐转运被非标记（冷）羊角酸盐和尿嘧啶剂苯溴马龙强烈抑制，被尿酸盐、烟酸盐和另一种尿嘧啶剂probenecid适度抑制。这是首次报道表明hURAT1介导旋转蛋白的转运。hURAT1可能是肾近端小管细胞的入口通路之一。
Orotate is a precursor of pyrimidine synthesis. The kidney uses exogenous orotate for the synthesis of uridine diphosphosugars, which are used in the glycosylation of collagen in glomerular and tubular basement membranes. Orotate uptake occurs in the liver and kidney, but its molecular mechanism is largely unknown. Since orotate has been shown to be a substrate of the renal urate/anion exchanger in brush border membrane vesicle studies, we investigated whether human URAT1 (hURAT1) mediates the transport of orotate using HEK293 cells expressing hURAT1 (HEK-hURAT1). hURAT1 mediated a time- and dose-dependent uptake of orotate (K(m) 5.2 mu M). hURAT1-mediated [(3)H] orotate transport was inhibited strongly by non-labeled (cold) orotate and the uricouric agent benzbromarone, and moderately inhibited by urate, nicotinate, and another uricouric agent, probenecid. This is the first report demonstrating that hURAT1 mediates the transport of orotate. hURAT1 may function as one of the entrance pathways in renal proximal tubular cells.