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9.B.9 The Urate Transporter (UAT) Family

Several reports have p;rovided evidence for a putative urate transporter (UAT) which was reported to catalyze the electrogenic efflux of urate from mammalian cells following degradation of the purine bases, adenine and guanine, to uric acid. A cDNA was isolated which encodes a protein of 322 amino acids. It is largely hydrophilic and is identical to a family of galactose binding lectins, the galectins. The selective urate transport activity of the recombinant UAT was reconstituted in planar lipid bilayers. One report, based on bioinformatic studies, concluded that there are four TMSs (Leal-Pinto et al. 1999).

Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia (Xu et al. 2017). A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein (Xu et al. 2017). Long term high fructose diet induced metabolic syndrome with increased blood pressure and proteinuria in rats. Metabolic syndrome was associated with dual increase in renal glucose and uric acid transporters, including SGLT1, SGLT2, GLUT2, GLUT9 and UAT (Ng et al. 2018).

The proposed transport reaction catalyzed by UAT is:

urate (in) urate (out)

 

References associated with 9.B.9 family:

Leal-Pinto, E., B.E. Cohen, and R.G. Abramson. (1999). Functional analysis and molecular modeling of a cloned urate transporter/channel. J. Membr. Biol. 169: 13-27. 10227848
Leal-Pinto, E., B.E. Cohen, M.S. Lipkowitz, and R.G. Abramson. (2002). Functional analysis and molecular model of the human urate transporter/channel, hUAT. Am. J. Physiol. Renal Physiol 283: F150-163. 12060597
Leal-Pinto, E., W. Tao, J. Rappaport, M. Richardson, B.A. Knorr, and R.G. Abramson. (1997). Molecular cloning and functional reconstitution of a urate transporter/channel. J. Biol. Chem. 272: 617-625. 8995305
Lipkowitz, M.S., E. Leal-Pinto, B.E. Cohen, and R.G. Abramson. (2002). Galectin 9 is the sugar-regulated urate transporter/channel UAT. Glycoconj J 19: 491-498. 14758072
Ng, H.Y., Y.T. Lee, W.H. Kuo, P.C. Huang, W.C. Lee, and C.T. Lee. (2018). Alterations of Renal Epithelial Glucose and Uric Acid Transporters in Fructose Induced Metabolic Syndrome. Kidney Blood Press Res 43: 1822-1831. 30537749
Rappoport, J.Z., M.S. Lipkowitz, and R.G. Abramson. (2001). Localization and topology of a urate transporter/channel, a galectin, in epithelium-derived cells. Am. J. Physiol. Cell Physiol. 281: C1926-1939. 11698251
Vollmer, W., M. von Rechenberg, and J.V. Höltje. (1999). Demonstration of molecular interactions between the murein polymerase PBP1B, the lytic transglycosylase MltA, and the scaffolding protein MipA of Escherichia coli. J. Biol. Chem. 274: 6726-6734. 10037771
Xu, L., Y. Shi, S. Zhuang, and N. Liu. (2017). Recent advances on uric acid transporters. Oncotarget 8: 100852-100862. 29246027