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Veterans Affairs Medical Center and School of Medicine, University of California, San Diego, California 92161
Inorganic pyrophosphate (PPi) regulates certain intracellular functions and extracellular crystal deposition. PPi is produced, degraded, and transported by specialized mechanisms. Moreover, dysregulated cellular PPi production, degradation, and transport all have been associated with disease, and PPi appears to directly mediate specific disease manifestations. In addition, natural and synthetic analogs of PPi are in use or currently under evaluation as prophylactic agents or therapies for disease. This review summarizes recent developments in the understanding of how PPi is made and disposed of by cells and assesses the body of evidence for potentially significant physiological functions of intracellular PPi in higher organisms. Major topics addressed are recent lines of molecular evidence that directly link decreased and increased extracellular PPi levels with diseases in which connective tissue matrix calcification is disordered. To illustrate in depth the effects of disordered PPi metabolism, this review weighs the roles in matrix calcification of the transmembrane protein ANK, which regulates intracellular to extracellular movement of PPi, and the PPi-generating phosphodiesterase nucleotide pyrophosphatase family isoenzyme plasma cell membrane glycoprotein-1 (PC-1).
PC-1; ANK; alkaline phosphatase; inorganic pyrophosphatase; chondrocalcinosis; hydroxyapatite
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