Litman Thomas, Søgaard Rikke, Zeuthen Thomas
Exiqon A/S, Department of Biomarker Discovery, Bygstubben 16, Vedbaek, 2950, Denmark.
Handb Exp Pharmacol. 2009(190):327-58. doi: 10.1007/978-3-540-79885-9_17.
The human aquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to ammonia, and AQP7, AQP9, and possibly AQP3, are permeable to urea. In humans, these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and the urea transporters (UTs). The mechanism by which ammonium is transported by aquaporins is not fully resolved. A comparison of transport equations, models, and experimental data shows that ammonia is transported in its neutral form, NH(3). In the presence of NH(3), the aquaporin stimulates H(+) transport. Consequently, this transport of H(+) is only significant at alkaline pH. It is debated whether the H(+) ion passes via the aquaporin or by some external route; the investigation of this problem requires the aquaporin-expressing cell to be voltage-clamped. The ammonia-permeable aquaporins differ from other aquaporins by having a less restrictive aromatic/arginine region, and an exclusively water-permeable aquaporin can be transformed into an ammonia-permeable aquaporin by single point mutations in this region. The ammonia-permeable aquaporins fall into two groups: those that are permeable (AQP3, 7, 9, 10) and those that are impermeable (AQP8) to glycerol. The two groups differ in the amino acid composition of their aromatic/arginine regions. The location of the ammonia-permeable aquaporins in the body parallels that of the Rh proteins. This applies to erythrocytes and to cells associated with nitrogen homeostasis and high rates of anabolism. In the liver, AQPs 8 and 9 are found together with Rh proteins in cells exposed to portal blood coming from the intestine. In the kidney, AQP3 might participate in the excretion of NH(4) (+) in the collecting duct. The interplay between the ammonia-permeable aquaporins and the other types of ammonia- and urea-permeable proteins is not well understood.
人类水通道蛋白AQP3、AQP7、AQP8、AQP9以及可能的AQP10可通透氨，而AQP7、AQP9以及可能的AQP3可通透尿素。在人类中，这些水通道蛋白补充了恒河猴（Rh）蛋白和尿素转运体（UTs）的氨转运功能。水通道蛋白转运铵的机制尚未完全阐明。对转运方程、模型和实验数据的比较表明，氨以中性形式NH(3)进行转运。在存在NH(3)的情况下，水通道蛋白会刺激H(+)转运。因此，这种H(+)转运仅在碱性pH值下较为显著。目前对于H(+)离子是通过水通道蛋白还是通过其他外部途径转运存在争议；对此问题的研究需要对表达水通道蛋白的细胞进行电压钳制。可通透氨的水通道蛋白与其他水通道蛋白的不同之处在于其芳香族/精氨酸区域限制较少，并且通过在该区域进行单点突变，仅能通透水的水通道蛋白可转变为可通透氨的水通道蛋白。可通透氨的水通道蛋白可分为两组：可通透甘油的（AQP3、7、9、10）和不可通透甘油的（AQP8）。这两组在其芳香族/精氨酸区域的氨基酸组成上有所不同。可通透氨的水通道蛋白在体内的定位与Rh蛋白相似。这适用于红细胞以及与氮稳态和高合成代谢率相关的细胞。在肝脏中，AQP8和AQP9与Rh蛋白共同存在于暴露于来自肠道的门静脉血的细胞中。在肾脏中，AQP3可能参与集合管中NH(4)(+)的排泄。可通透氨的水通道蛋白与其他类型的可通透氨和尿素的蛋白之间的相互作用尚不清楚。
