Hediger M A
Membrane Biology Program & Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ther Umsch. 2004 Sep;61(9):541-5. doi: 10.1024/0040-5930.61.9.541.
In humans, uric acid is the final breakdown product of unwanted purine nucleotides. Uric acid is the last stage in purine degradation, because humans lack the enzyme uricase which converts uric acid into allantoin. Uric acid has profound beneficial effects since it scavenges potential harmful radicals in our body. However, in conjunction with genetic or environmental factors, uric acid can cause significant health problems, leading to kidney stones when it builds up in the kidneys and to gout when crystals accumulate in the joints. The levels of uric acid in the blood must be tightly controlled to minimize these detrimental effects. Normally, the body eliminates enough uric acid in the kidney, and in part also through the intestines, to keep its concentration at a healthy level in the blood (approximately 300 microM). In patients with gout or kidney stone disease, however, the body either produces excessive amounts of uric acid or its ability to eliminate uric acid is disturbed in some way. In the kidney, uric acid is reabsorbed via the uric acid transporter URAT1. This transporter is the major mechanism for regulating blood uric acid levels and therefore may prove an interesting target for future drug development.
在人类体内,尿酸是无用嘌呤核苷酸的最终分解产物。尿酸是嘌呤降解的最后阶段,因为人类缺乏将尿酸转化为尿囊素的尿酸酶。尿酸具有深远的有益作用,因为它能清除我们体内潜在的有害自由基。然而,与遗传或环境因素共同作用时,尿酸会引发严重的健康问题,当它在肾脏中积聚时会导致肾结石,当晶体在关节中积累时会导致痛风。必须严格控制血液中的尿酸水平,以将这些有害影响降至最低。正常情况下,身体通过肾脏以及部分通过肠道消除足够的尿酸,以使血液中的尿酸浓度保持在健康水平(约300微摩尔)。然而,在痛风或肾结石疾病患者中,身体要么产生过量的尿酸,要么其消除尿酸的能力在某种程度上受到干扰。在肾脏中,尿酸通过尿酸转运体URAT1被重吸收。这种转运体是调节血液尿酸水平的主要机制,因此可能成为未来药物开发的一个有趣靶点。