title: Molecular identification of a renal urate anion exchanger that regulates blood urate levels.
abstract: Urate, a naturally occurring product of purine metabolism, is a scavenger of biological oxidants implicated in numerous disease processes, as demonstrated by its capacity of neuroprotection. It is present at higher levels in human blood (200 500 microM) than in other mammals, because humans have an effective renal urate reabsorption system, despite their evolutionary loss of hepatic uricase by mutational silencing. The molecular basis for urate handling in the human kidney remains unclear because of difficulties in understanding diverse urate transport systems and species differences. Here we identify the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted by uricosuric and antiuricosuric agents (which affect excretion of uric acid). Moreover, we provide evidence that patients with idiopathic renal hypouricaemia (lack of blood uric acid) have defects in SLC22A12. Identification of URAT1 should provide insights into the nature of urate homeostasis, as well as lead to the development of better agents against hyperuricaemia, a disadvantage concomitant with human evolution.
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Arthit
authors.initials: A
authors.lastname: Chairoungdua
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shigeta
authors.forename: Promsuk
authors.initials: P
authors.lastname: Jutabha
authors.forename: Seok Ho
authors.initials: SH
authors.lastname: Cha
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Michio
authors.initials: M
authors.lastname: Takeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Oda
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Niwa
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000097:blood* / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism; D014981:Xenopus
chemical_list: D000838:Anions; D002352:Carrier Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C491241:SLC22A12 protein, human; C103862:urate transporter; D014527:Uric Acid