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Inorganic pyrophosphate generation and disposition in pathophysiology Terkeltaub RAAm J Physiol Cell Physiol 2001[Jul]; 281 (1): C1-C11Inorganic pyrophosphate (PP(i)) regulates certain intracellular functions and extracellular crystal deposition. PP(i) is produced, degraded, and transported by specialized mechanisms. Moreover, dysregulated cellular PP(i) production, degradation, and transport all have been associated with disease, and PP(i) appears to directly mediate specific disease manifestations. In addition, natural and synthetic analogs of PP(i) are in use or currently under evaluation as prophylactic agents or therapies for disease. This review summarizes recent developments in the understanding of how PP(i) is made and disposed of by cells and assesses the body of evidence for potentially significant physiological functions of intracellular PP(i) in higher organisms. Major topics addressed are recent lines of molecular evidence that directly link decreased and increased extracellular PP(i) levels with diseases in which connective tissue matrix calcification is disordered. To illustrate in depth the effects of disordered PP(i) metabolism, this review weighs the roles in matrix calcification of the transmembrane protein ANK, which regulates intracellular to extracellular movement of PP(i), and the PP(i)-generating phosphodiesterase nucleotide pyrophosphatase family isoenzyme plasma cell membrane glycoprotein-1 (PC-1).|*Phosphoric Diester Hydrolases[MESH]|Animals[MESH]|Calcification, Physiologic/physiology[MESH]|Calcinosis/*physiopathology[MESH]|Connective Tissue Cells/*metabolism[MESH]|Diphosphates/chemistry/*metabolism[MESH]|Humans[MESH]|Membrane Glycoproteins/genetics/*metabolism[MESH]|Membrane Proteins/*metabolism[MESH]|Molecular Structure[MESH]|Phosphate Transport Proteins[MESH]|Pyrophosphatases/genetics/metabolism[MESH] |
