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Pathway Description
Phosphatidylinositol Phosphate Metabolism
Homo sapiens
Metabolic Pathway
Phosphatidylinositol phosphates, or phosphoinositides, are intracellular signaling lipids. Seven different phosphoinositides have been identified in mammals, each distinguished by the number and/or position of the phosphate groups on the inositol ring. The inositol can be mono-, di-, or triphosphorylated, with the remaining phosphoinositides being isomers of these three forms. Phosphoinositides regulate a variety of signal transduction processes, thus playing a number of important roles in the cell, such as actin cytoskeletal reorganization, membrane transport, and cell proliferation. They may also affect protein localization, aggregation, and activity by acting as secondary messengers. The ability of the cell to recognize the different types of phosphoinositides as different cellular signals means that their synthesis and metabolism must be tightly regulated. Synthesis begins with the attachment of an inositol phosphate head group to diacylglycerol via a phospholipase C enzyme, creating a phosphoinositide. Conversion between the different types of phosphoinositides is then done by a number of specific phosphoinositide kinases and phosphatases, which add (kinase) and remove (phosphatase) phosphates from the inositol ring. The specific localization and regulation of the phosphoinositide kinases and phosphatases thus controls the activity of the phosphoinositides. While the phosphoinositides are always located in the membrane, their particular kinases and phosphatases may be found in the cytoplasm or in the membrane of the cell or cell organelles.
References
Phosphatidylinositol Phosphate Metabolism References
Abel K, Anderson RA, Shears SB: Phosphatidylinositol and inositol phosphate metabolism. J Cell Sci. 2001 Jun;114(Pt 12):2207-8.
Pubmed: 11493657
Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC: Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J Biol Chem. 1999 Apr 9;274(15):9907-10.
Pubmed: 10187762
De Matteis MA, Di Campli A, Godi A: The role of the phosphoinositides at the Golgi complex. Biochim Biophys Acta. 2005 Jul 10;1744(3):396-405. doi: 10.1016/j.bbamcr.2005.04.013.
Pubmed: 15979509
Giudici ML, Hinchliffe KA, Irvine RF: Phosphatidylinositol phosphate kinases. J Endocrinol Invest. 2004;27(6 Suppl):137-42.
Pubmed: 15481814
Kanaho Y, Suzuki T: Phosphoinositide kinases as enzymes that produce versatile signaling lipids, phosphoinositides. J Biochem. 2002 Apr;131(4):503-9.
Pubmed: 11926986
Poccia D, Larijani B: Phosphatidylinositol metabolism and membrane fusion. Biochem J. 2009 Mar 1;418(2):233-46. doi: 10.1042/BJ20082105.
Pubmed: 19196244
Sasaki T, Takasuga S, Sasaki J, Kofuji S, Eguchi S, Yamazaki M, Suzuki A: Mammalian phosphoinositide kinases and phosphatases. Prog Lipid Res. 2009 Nov;48(6):307-43. doi: 10.1016/j.plipres.2009.06.001. Epub 2009 Jul 4.
Pubmed: 19580826
Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, Woscholski R, Parker PJ, Waterfield MD: Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem. 2001;70:535-602. doi: 10.1146/annurev.biochem.70.1.535.
Pubmed: 11395417
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