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This Article Full Text Full Text (PDF) All Versions of this Article: 93/1/43    most recent expphysiol.2007.040790v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moochhala, S. H. Articles by Simmons, N. L. Search for Related Content PubMed PubMed Citation Articles by Moochhala, S. H. Articles by Simmons, N. L. Related Collections Hot Topic Reviews

¹ Epithelial Research Group, Institute for Cell and Molecular Biosciences, Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK ² Institute of Human Genetics, International Centre for Life, Central Parkway, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 3BZ, UK

Extracellular pyrophosphate (PP_i) plays a central role in the control of normal bone mineralization since it antagonizes inorganic phosphate in the promotion of hydroxyapatite deposition. Studies using knock-out mice have established the functional importance of PP_i generation via nucleotide pyrophosphatase phosphodiesterases (NPP) and of PP_i transmembrane transport by the progressive ankylosis (ANK) protein. Tissue non-specific alkaline phosphatase activity counteracts this by hydrolysis of PP_i to inorganic phosphate. The molecular nature and transport function of ANK are reviewed. A close parallel is drawn between the controlled mineralization of bone and the prevention of abnormal calcium crystal deposition within the kidney, especially when concentrated urine is produced. Pyrophosphate is present in urine, and ANK is expressed in the cortical collecting duct where PP_i transport to both the tubular lumen and the renal interstitium may occur. Pyrophosphate may also be generated here by nucleoside triphosphate diphosphohydrolases (NTPD2 and 3) together with NPP1. Alkaline phosphatase activity is restricted to the proximal nephron, remote from these sites of PP_i generation, transport and function. The physiological importance of PP_i generation and transport in preventing idiopathic calcium renal stone disease and nephrocalcinosis now needs to be established.

(Received 21 September 2007; accepted after revision 2 October 2007; first published online 2 October 2007)
Corresponding author N. L. Simmons: Epithelial Research Group, Institute for Cell and Molecular Biosciences, Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, UK. Email: n.l.simmons{at}ncl.ac.uk