Anzai Naohiko, Enomoto Atsushi, Endou Hitoshi
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan.
Curr Rheumatol Rep. 2005 Jun;7(3):227-34. doi: 10.1007/s11926-996-0044-0.
Urate is the major inert end product of purine degradation in higher primates in contrast to most other mammals because of the genetic silencing of hepatic oxidative enzyme uricase. The kidney plays a dominant role in urate elimination. The kidney excretes 70% of the daily urate production. Therefore, it is important to understand renal urate handling mechanism because the under excretion of urate has been implicated in the development of hyperuricemia that leads to gout. The urate transport systems exist in the proximal tubule but they are complicated because of their bidirectional transport and the species differences. Recently, we have identified the urate-anion exchanger URAT1 (SLC22A12) in the human kidney and found that defects in SLC22A12 lead to idiopathic renal hypouricemia. URAT1 is targeted by uricosuric and antiuricosuric agents that affect urate excretion. Molecular identification of urate transporting proteins will lead to the new drug development for hyperuricemia.
由于肝脏氧化酶尿酸酶的基因沉默，与大多数其他哺乳动物不同，尿酸是高等灵长类嘌呤降解的主要惰性终产物。肾脏在尿酸排泄中起主导作用。肾脏排泄每日产生尿酸的70%。因此，了解肾脏尿酸处理机制很重要，因为尿酸排泄不足与导致痛风的高尿酸血症的发生有关。尿酸转运系统存在于近端小管中，但由于其双向转运和物种差异而较为复杂。最近，我们在人肾脏中鉴定出尿酸 - 阴离子交换体URAT1（SLC22A12），并发现SLC22A12缺陷会导致特发性肾性低尿酸血症。URAT1是影响尿酸排泄的促尿酸排泄药和抗促尿酸排泄药的作用靶点。尿酸转运蛋白的分子鉴定将导致高尿酸血症新药的开发。
