抄録
Orotic acid, a normal intermediate in pyrimidine synthesis, is converted to uridine 5'-triphosphate (UTP) that is utilized for the sythesis of RNA and for uridine diphosphosugars (UDP sugars) used in the glycosylation of basement membrane collagen. Therefore, as a precursor of uridine nucleotides, orotic acid incorporation is an important factor in glomerular and tubular basement membrane thickening, for example, observed in diabetes-induced renal hypertrophy. Orotic acid uptake is observed in normal liver and kidney, but its molecular mechanism is largely unknown. Because orotic acid is also known as a substrate of renal urate/anion exchanger, we investigated whether human renal urate transporter URAT1 mediates the transport of orotic acid using HEK293 cells expressing hURAT1 (HEK293-URAT1). Human URAT1 mediated a time- and dose-dependent uptake of orotic acid, with Km values of 5.2 μM. URAT1-mediated orotic acid transport was inhibited strongly by orotic acid and benzbromarone and moderately by uric acid, nicotinic acid, and probenecid. These results suggest that human URAT1 mediates the transport of orotic acid, and may function as one of its entrance pathway in the renal proximal tubular cells. [J Physiol Sci. 2007;57 Suppl:S76]
