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Pathway Description
Inositol Metabolism
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-09-15
The carbocyclic polyol inositol (otherwise known as myo-inositol) has a significant role in physiological systems as many secondary eukaryotic messengers derive their structure from inositol. Examples of secondary messengers derived from inositol include inositol phosphates, phosphatidylinositol (PI), and phosphatidylinositol phosphate (PIP) lipids.
Inositol is abundant in many commonly consumed foods such as bran-rich cereals, beans, nuts, and fruit (particularly cantaloupe, melons, and oranges). It can also be synthesized by the body through the conversion of glucose-6-phosphate into mho-inositol under the following pathway: (1) glucose-6-phosphate undergoes isomerization due to the action of inositol-3-phosphate synthase (ASYNA1) which produces myo-inositol 3-phosphate; (2) myo-inositol 3-phosphate undergoes dephosphorylation via the action of inositol monophosphatase (IMPase 1) to produce myo-inositol. From this point, myo-inositol can move through multiple different fates depending on the secondary messenger being synthesized. For phosphatidyliositol, phosphatidylinositol synthase generates it with the substrates CDP-diacylglycerol and myo-inositol. Phosphatidyliositol can be modified further to generate phosphatidylinositol phosphate lipids via the action of class I, II and III phosphoinositide 3-kinases (PI 3-kinases). Other messengers (i.e. inositol phosphates) can be produced with the phospholipase C-mediated hydrolysis of phosphatidylinositol phosphates or with the action of other enzymes that remove or add phosphate groups.
References
Inositol Metabolism References
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, Osoegawa K, Zhu B, Marra M, Schein J, Bosdet I, Fjell C, Jones S, Krzywinski M, Mathewson C, Siddiqui A, Wye N, McPherson J, Zhao S, Fraser CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Worley KC, Cooney AJ, D'Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Venter JC, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F: Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493-521. doi: 10.1038/nature02426.
Pubmed: 15057822
Takazawa K, Vandekerckhove J, Dumont JE, Erneux C: Cloning and expression in Escherichia coli of a rat brain cDNA encoding a Ca2+/calmodulin-sensitive inositol 1,4,5-trisphosphate 3-kinase. Biochem J. 1990 Nov 15;272(1):107-12. doi: 10.1042/bj2720107.
Pubmed: 2176078
Choi KY, Kim HK, Lee SY, Moon KH, Sim SS, Kim JW, Chung HK, Rhee SG: Molecular cloning and expression of a complementary DNA for inositol 1,4,5-trisphosphate 3-kinase. Science. 1990 Apr 6;248(4951):64-6. doi: 10.1126/science.2157285.
Pubmed: 2157285
Communi D, Lecocq R, Vanweyenberg V, Erneux C: Active site labelling of inositol 1,4,5-trisphosphate 3-kinase A by phenylglyoxal. Biochem J. 1995 Aug 15;310 ( Pt 1):109-15. doi: 10.1042/bj3100109.
Pubmed: 7646431
Lopez-Coronado JM, Belles JM, Lesage F, Serrano R, Rodriguez PL: A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. J Biol Chem. 1999 Jun 4;274(23):16034-9. doi: 10.1074/jbc.274.23.16034.
Pubmed: 10347153
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Patel S, Yenush L, Rodriguez PL, Serrano R, Blundell TL: Crystal structure of an enzyme displaying both inositol-polyphosphate-1-phosphatase and 3'-phosphoadenosine-5'-phosphate phosphatase activities: a novel target of lithium therapy. J Mol Biol. 2002 Jan 25;315(4):677-85. doi: 10.1006/jmbi.2001.5271.
Pubmed: 11812139
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Lemaire JF, McPherson PS: Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a new internal PDZ-recognition motif. FEBS Lett. 2006 Dec 22;580(30):6948-54. doi: 10.1016/j.febslet.2006.11.061. Epub 2006 Dec 4.
Pubmed: 17161399
Davy BE, Robinson ML: Congenital hydrocephalus in hy3 mice is caused by a frameshift mutation in Hydin, a large novel gene. Hum Mol Genet. 2003 May 15;12(10):1163-70. doi: 10.1093/hmg/ddg122.
Pubmed: 12719380
Row PE, Reaves BJ, Domin J, Luzio JP, Davidson HW: Overexpression of a rat kinase-deficient phosphoinositide 3-kinase, Vps34p, inhibits cathepsin D maturation. Biochem J. 2001 Feb 1;353(Pt 3):655-61. doi: 10.1042/0264-6021:3530655.
Pubmed: 11171063
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000011
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