| Author |
Yamamoto S, Inoue K, Yasujima T, Takei H, Yamashiro T, Asai K, Matake I, Uchiyama S, Ohta K, Kishimoto H, Higuchi K, Anayama H, Asao Y, Hirabayashi H, Amano N, Shimizu T, Takada T, Tamura T, Wakai K, Kawamura Y, Nakayama A, Toyoda Y, Matsuo H, Yuasa H.
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| Abstract |
Serum urate levels are high in hominoids because of the evolutionary loss of uricase, an enzyme involved in purine metabolism during evolution. However, the mechanism underlying uricase loss remains unclear. We report the involvement of the neofunctionalized solute carrier family 52 member A1 (SLC52A1) in the evolutionary loss of uricase. Synteny analysis revealed that SLC52A1 was duplicated from SLC52A2, which encodes a riboflavin transporter and is conserved among primates. Functional studies demonstrated the ability of primate SLC52A1 to transport urate as well as riboflavin and the mediation of cellular uptake and efflux of urate by human SLC52A1 through facilitated diffusion. Transcellular transport studies demonstrated that SLC52A1, which is basolaterally localized in enterocytes, works synergistically with ABC subfamily G member 2, a luminally localized urate efflux transporter, to remove urate from the basolateral side. Before uricase loss, acquiring SLC52A1 may have provided primates with a novel intestinal urate transport system and allowed for evolutionary uricase loss in hominoids.
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