Human urate transporter 1 (hURAT1) mediates the transport of orotate.
Summary of "Human urate transporter 1 (hURAT1) mediates the transport of orotate."
Orotate is a precursor of pyrimidine synthesis. The kidney uses exogenous orotate for the synthesis of uridine diphosphosugars, which are used in the glycosylation of collagen in glomerular and tubular basement membranes. Orotate uptake occurs in the liver and kidney, but its molecular mechanism is largely unknown. Since orotate has been shown to be a substrate of the renal urate/anion exchanger in brush border membrane vesicle studies, we investigated whether human URAT1 (hURAT1) mediates the transport of orotate using HEK293 cells expressing hURAT1 (HEK-hURAT1). hURAT1 mediated a time- and dose-dependent uptake of orotate (K (m) 5.2 μM). hURAT1-mediated [(3)H]orotate transport was inhibited strongly by non-labeled (cold) orotate and the uricouric agent benzbromarone, and moderately inhibited by urate, nicotinate, and another uricouric agent, probenecid. This is the first report demonstrating that hURAT1 mediates the transport of orotate. hURAT1 may function as one of the entrance pathways in renal proximal tubular cells.
Affiliation
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Journal Details
This article was published in the following journal.
Name: The journal of physiological sciences : JPS
ISSN: 1880-6562
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21350910
- DOI: http://dx.doi.org/10.1007/s12576-011-0136-0
Medical and Biotech [MESH] Definitions
Glucose Transporter Type 5
A hexose transporter that mediates FRUCTOSE transport in SKELETAL MUSCLE and ADIPOCYTES and is responsible for luminal uptake of dietary fructose in the SMALL INTESTINE.
Organic Anion Transport Polypeptide C
An organic anion transporter found in human liver. It is capable of transporting a variety organic anions and mediates sodium-independent uptake of bile in the liver.
Organic Anion Transport Protein 1
A polyspecific transporter for organic cations found primarily in the kidney. It mediates the coupled exchange of alpha-ketoglutarate with organic ions such as P-AMINOHIPPURIC ACID.
Cationic Amino Acid Transporter 2
A high-affinity, low capacity system y+ amino acid transporter with strong similarity to CATIONIC AMINO ACID TRANSPORTER 1. The two isoforms of the protein, CAT-2A and CAT-2B, exist due to alternative mRNA splicing. The transporter has specificity for the transport of ARGININE; LYSINE; and ORNITHINE.
Proton-coupled Folate Transporter
A symporter protein that couples the transport of FOLIC ACID with HYDROGEN IONS. The transporter functions most effectively under acidic conditions.
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