Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies.
Summary of "Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies."
Humans have higher serum uric acid levels than other mammalian species owing to the genetic silencing of the hepatic enzyme uricase that metabolizes uric acid into allantoin. Urate (the ionized form of uric acid) is generated from purine metabolism and it may provide antioxidant defense in the human body. Despite its potential advantage, sustained hyperuricemia has pathogenetic causes in gout and renal diseases, and putative roles in hypertension and cardiovascular diseases. Since the kidney plays a dominant role in maintaining plasma urate levels through the excretion process, it is important to understand the molecular mechanism of renal urate handling. Although the molecular identification of a kidney-specific urate/anion exchanger URAT1 in 2002 paved the way for successive identification of several urate transport-related proteins, the entire picture of effective renal urate handling in humans has not yet been clarified. Recently, several genome-wide association studies identified a substantial association between uric acid concentration and single nucleotide polymorphisms in at least ten genetic loci including eight transporter-coding genes. In 2008, we functionally characterized the facilitatory glucose transporter family member SLC2A9 (GLUT9), one of the candidate genes for urate handling, as a voltage-driven urate transporter URATv1 at the basolateral side of renal proximal tubules that comprises the main route of the urate reabsorption pathway, in tandem with URAT1 at the apical side. In this review, recent findings concerning these candidate molecules are presented.
Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan, email@example.com.
This article was published in the following journal.
Name: Clinical and experimental nephrology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22038265
- DOI: http://dx.doi.org/10.1007/s10157-011-0532-z
Medical and Biotech [MESH] Definitions
Organic Anion Transporters, Atp-dependent
A subclass of ORGANIC ANION TRANSPORTERS whose transport of organic anions is linked directly to the hydrolysis of ATP. The subclass includes those ATP-BINDING CASSETTE TRANSPORTERS that transport organic ions.
Education, Dental, Continuing
Educational programs designed to inform dentists of recent advances in their fields.
Education, Nursing, Continuing
Educational programs designed to inform nurses of recent advances in their fields.
Education, Medical, Continuing
Educational programs designed to inform physicians of recent advances in their field.
Education, Pharmacy, Continuing
Educational programs designed to inform graduate pharmacists of recent advances in their particular field.
The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elev...
Characterization of Cellular Uptake of Perfluorooctanoate via Organic Anion Transporting Polypeptide 1A2, Organic Anion Transporter 4, and Urate Transporter 1 for Their Potential Roles in Mediating Human Renal Reabsorption of Perfluorocarboxylates.
It has been hypothesized that human renal apical membrane transporters play a key role in human renal reabsorption of perfluorooctanoate (PFO), which contributes to the long half-life of PFO in humans...
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 tubula...
This highlight examines recent advances in the development of synthetic membrane transporters for anions, highlighting the underlying principles of transporter design and the promising applications of...
The approval of febuxostat, a non-purine-analogue inhibitor of xanthine oxidase, by the European Medicines Agency and the US Food and Drug Administration heralds a new era in the treatment of gout. Th...
Transporters in kidney are critical in detoxification and elimination of xenobiotics from systemic circulation, and thus are major determinants of drug response and sensitivity. Transporte...
Previous studies in animals revealed, that the activity of certain transporters along the nephron is changed with acute rejection after renal transplantation. We intend to investigate unde...
Recent advances in critical care medicine have dramatically improved morbidity and mortality of critical illness. Goal-directed therapy protocols have been instrumental in this change. Goa...
The purpose of this study is to evaluate the use of the VersaMed iVent ventilator in the acute care setting, hypothesizing that, in comparison to the standard approach, the use of the Vers...
The purpose of this study is to determine the effect of febuxostat, once daily (QD) or twice daily (BID), on renal function in gout subjects with elevated serum urate levels and who have...