Urate transporters: an evolving field

Abstract

Urate (uric acid) is the end product of purine metabolism in human beings owing to the genetic loss of hepatic urate oxidase (uricase). Despite its potential advantage as an antioxidant, sustained hyperuricemia is associated with gout, renal diseases, hypertension, and cardiovascular diseases. Because the kidney plays a dominant role in maintaining serum urate levels through its excretion, it is important to understand the molecular mechanism of renal urate handling. Although molecular identification of the urate/anion exchanger URAT1 (SLC22A12) in 2002 paved the way for successive identification of several urate transport-related proteins, the entire picture of effective renal urate handling in human beings has not yet been clarified. Recently, several genome-wide association studies have revealed close associations between serum urate levels and single nucleotide polymorphisms in at least 10 genetic loci including eight transporter-related genes. These findings led us to consider the roles of urate transporters in extrarenal tissues such as the intestine. In this review, we discuss various aspects of transmembrane transport of urate in the human body.