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)