Uric acid transport.
OBJECTIVE
The goal of this article is to review the physiology and describe newly defined molecular mechanisms that are responsible for renal urate transport.


RESULTS
Four complementary DNAs have recently been cloned whose expressed proteins transport urate. Two of these proteins have been localized to the apical membrane of proximal tubular cells: one, a urate transporter/channel, a galectin, is an electrogenic transporter (an ion channel); the second is a urate-anion electroneutral exchanger, a member of the organic anion transporter family. The other urate transport proteins, organic anion transporters 1 and 3, are also members of the organic anion transporter family. These proteins have been localized to the basolateral membrane of proximal tubular cells: organic anion transporter 1 is an electroneutral organic anion exchanger; the mechanism of urate transport on organic anion transporter 3 remains to be determined.


CONCLUSIONS
The molecular definition and localization of four urate transport proteins provides a basis for developing a molecular model of the bi-directional transport of urate in renal proximal tubules. It seems likely that the urate-anion exchanger is responsible for luminal reabsorption while the urate transporter/channel permits secretion of urate from the cell into the lumen. Since organic anion transporters 1 and 3 reside in the basolateral membrane, one or both may be relevant in the reabsorptive flux of urate into the peritubular capillary as well as in the cellular uptake of urate from the peritubular space, the first step in the process of urate secretion. Knowledge of the molecular basis of urate transport should provide greater insights into states of altered transport as well as assist in development of drugs to modify urate flux.
Rafey
Mohammed A
MA
Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Lipkowitz
Michael S
MS
Leal-Pinto
Edgar
E
Abramson
Ruth G
RG
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008958:Models, Molecular; D014527:Uric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D014527:Uric Acid