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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: myo-inositol biosynthesis

Enzyme View:

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Secondary Metabolites Biosynthesis Sugar Derivatives Biosynthesis Cyclitols Biosynthesis myo-Inositol Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col Inferred from experiment [Donahue10], Archaeoglobus fulgidus , Bacteroides thetaiotaomicron , Homo sapiens , Methanocaldococcus jannaschii , Mycobacterium smegmatis , Mycobacterium tuberculosis , Mycobacterium tuberculosis H37Rv , Novosphingobium aromaticivorans , Pantoea agglomerans , Pseudomonas syringae , Sulfolobus solfataricus , Thermotoga maritima , Thermotoga neapolitana

Expected Taxonomic Range: Archaea , Bacteria , Eukaryota

Summary:
Inositol is the generic name for 1,2,3,4,5,6-cyclohexanehexol. Epimerization of the six hydroxyl groups results in nine stereoisomers. myo-Inositol is the physiologically most common tereoisomer and is abundantly (but not universally) distributed throughout much of the biological system.

myo-Inositol is an essential polyol in eukaryotes, where its phospholipid derivative phosphatidylinositol (PI) is an important constituent of phospholipid membranes. PI is also cleaved by phospholipase C to generate inositol phosphate (IP) and diacyglycerol, both of which are central cell signalling molecules.

In prokaryotes inositol is not as widely spread as in eukaryotes. While it is commonly found in archaebacteria, where its derivatives serve an important role in osmotic protection at high temperatures [Santos02a], it is absent (or present in very low amounts) from most eubacteria, with the exception of the Actinomycetales group, which includes the streptomycetes, corynebacteria and mycobacteria. In these organisms a phosphorylated inositol is an intermediate in the synthesis of a major thiol called mycothiol [Fahey01]. Mycothiol is important in maintaining the redox balance in the cell, in protection from oxidative stress, and in cysteine storage. In addition, the corynebacteria and mycobacteria produce several cell wall lipoglycans from PI. In these compounds the lipid moieties which are attached to the PI act as anchors in the cell envelope.

PI-containing molecules have been shown to be essential for growth of the fast-growing species Mycobacterium smegmatis, as mutants lacking PI synthase are not viable [Jackson00]. In most other eubacteria inositol compounds (small soluble molecules or lipids) are undetected or represent very minor components. Earlier work found that various strains of Escherichia coli, Salmonella enterica enterica serovar Typhimurium and Pseudomonas sp. did not contain any PI [Cronan72a, Lechevalier77]. Later work discovered readily measurable amounts of PI and PI synthase in Pseudomonas syringae, Pantoea agglomerans, and Ice+ strains of Escherichia coli (these are strains that promote ice-nucleation) [Kozloff91]. However, phosphatidylinositol in these Escherichia coli strains represents less than 0.01% of total phospholipid in the cells [Kozloff91].

In all myo-inositol-producing organisms studied to date myo-inositol is produced via dephosphorylation of L-myo-inositol 1-phosphate, which is generated from glucose 6-phosphate in a rate-limiting step by L-myo-inositol 1-phosphate synthase (MIPS).

Credits:
Created 17-Nov-2004 by Caspi R , SRI International


References

Cronan72a: Cronan JE, Vagelos PR (1972). "Metabolism and function of the membrane phospholipids of Escherichia coli." Biochim Biophys Acta 265(1);25-60. PMID: 4552305

Donahue10: Donahue JL, Alford SR, Torabinejad J, Kerwin RE, Nourbakhsh A, Ray WK, Hernick M, Huang X, Lyons BM, Hein PP, Gillaspy GE (2010). "The Arabidopsis thaliana Myo-inositol 1-phosphate synthase1 gene is required for Myo-inositol synthesis and suppression of cell death." Plant Cell 22(3);888-903. PMID: 20215587

Fahey01: Fahey RC (2001). "Novel thiols of prokaryotes." Annu Rev Microbiol 2001;55;333-56. PMID: 11544359

Jackson00: Jackson M, Crick DC, Brennan PJ (2000). "Phosphatidylinositol is an essential phospholipid of mycobacteria." J Biol Chem 275(39);30092-9. PMID: 10889206

Kozloff91: Kozloff LM, Turner MA, Arellano F, Lute M (1991). "Phosphatidylinositol, a phospholipid of ice-nucleating bacteria." J Bacteriol 173(6);2053-60. PMID: 1848220

Lechevalier77: Lechevalier MP (1977). "Lipids in bacterial taxonomy - a taxonomist's view." CRC Crit Rev Microbiol 5(2);109-210. PMID: 844323

Majumder03: Majumder AL, Chatterjee A, Ghosh Dastidar K, Majee M (2003). "Diversification and evolution of L-myo-inositol 1-phosphate synthase." FEBS Lett 553(1-2);3-10. PMID: 14550537

Santos02a: Santos H, da Costa MS (2002). "Compatible solutes of organisms that live in hot saline environments." Environ Microbiol 4(9);501-9. PMID: 12220406

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Arai07a: Arai R, Ito K, Ohnishi T, Ohba H, Akasaka R, Bessho Y, Hanawa-Suetsugu K, Yoshikawa T, Shirouzu M, Yokoyama S (2007). "Crystal structure of human myo-inositol monophosphatase 2, the product of the putative susceptibility gene for bipolar disorder, schizophrenia, and febrile seizures." Proteins 67(3);732-42. PMID: 17340635

Bachhawat99: Bachhawat N, Mande SC (1999). "Identification of the INO1 gene of Mycobacterium tuberculosis H37Rv reveals a novel class of inositol-1-phosphate synthase enzyme." J Mol Biol 291(3);531-6. PMID: 10448034

Bone92: Bone R, Springer JP, Atack JR (1992). "Structure of inositol monophosphatase, the putative target of lithium therapy." Proc Natl Acad Sci U S A 89(21);10031-5. PMID: 1332026

Bone94: Bone R, Frank L, Springer JP, Atack JR (1994). "Structural studies of metal binding by inositol monophosphatase: evidence for two-metal ion catalysis." Biochemistry 33(32);9468-76. PMID: 8068621

Chen00d: Chen L, Zhou C, Yang H, Roberts MF (2000). "Inositol-1-phosphate synthase from Archaeoglobus fulgidus is a class II aldolase." Biochemistry 39(40);12415-23. PMID: 11015222

Chen98: Chen L, Roberts MF (1998). "Cloning and expression of the inositol monophosphatase gene from Methanococcus jannaschii and characterization of the enzyme." Appl Environ Microbiol 64(7);2609-15. PMID: 9647837

Chen99c: Chen L, Roberts MF (1999). "Characterization of a tetrameric inositol monophosphatase from the hyperthermophilic bacterium Thermotoga maritima." Appl Environ Microbiol 65(10);4559-67. PMID: 10508089

Conklin06: Conklin PL, Gatzek S, Wheeler GL, Dowdle J, Raymond MJ, Rolinski S, Isupov M, Littlechild JA, Smirnoff N (2006). "Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic acid biosynthetic enzyme." J Biol Chem 281(23);15662-70. PMID: 16595667

Fischbach06: Fischbach A, Adelt S, Muller A, Vogel G (2006). "Disruption of inositol biosynthesis through targeted mutagenesis in Dictyostelium discoideum: generation and characterization of inositol-auxotrophic mutants." Biochem J 397(3);509-18. PMID: 16599905

Ganzhorn96: Ganzhorn AJ, Lepage P, Pelton PD, Strasser F, Vincendon P, Rondeau JM (1996). "The contribution of lysine-36 to catalysis by human myo-inositol monophosphatase." Biochemistry 35(33);10957-66. PMID: 8718889

Laing04: Laing WA, Bulley S, Wright M, Cooney J, Jensen D, Barraclough D, MacRae E (2004). "A highly specific L-galactose-1-phosphate phosphatase on the path to ascorbate biosynthesis." Proc Natl Acad Sci U S A 101(48);16976-81. PMID: 15550539

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Loewus84: Loewus MW, Bedgar DL, Loewus FA (1984). "1L-myo-inositol 1-phosphate synthase from pollen of Lilium longiflorum. An ordered sequential mechanism." J Biol Chem 259(12);7644-7. PMID: 6736020

McAllister92: McAllister G, Whiting P, Hammond EA, Knowles MR, Atack JR, Bailey FJ, Maigetter R, Ragan CI (1992). "cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme." Biochem J 284 ( Pt 3);749-54. PMID: 1377913

MGI: "MGI Database: Mouse Genome Informatics."

Movahedzadeh04: Movahedzadeh F, Smith DA, Norman RA, Dinadayala P, Murray-Rust J, Russell DG, Kendall SL, Rison SC, McAlister MS, Bancroft GJ, McDonald NQ, Daffe M, Av-Gay Y, Stoker NG (2004). "The Mycobacterium tuberculosis ino1 gene is essential for growth and virulence." Mol Microbiol 51(4);1003-14. PMID: 14763976

Norman02: Norman RA, McAlister MS, Murray-Rust J, Movahedzadeh F, Stoker NG, McDonald NQ (2002). "Crystal structure of inositol 1-phosphate synthase from Mycobacterium tuberculosis, a key enzyme in phosphatidylinositol synthesis." Structure (Camb) 10(3);393-402. PMID: 12005437

Ohnishi07: Ohnishi T, Ohba H, Seo KC, Im J, Sato Y, Iwayama Y, Furuichi T, Chung SK, Yoshikawa T (2007). "Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1." J Biol Chem 282(1);637-46. PMID: 17068342

Petersen10: Petersen LN, Marineo S, Mandala S, Davids F, Sewell BT, Ingle RA (2010). "The missing link in plant histidine biosynthesis: Arabidopsis myoinositol monophosphatase-like2 encodes a functional histidinol-phosphate phosphatase." Plant Physiol 152(3);1186-96. PMID: 20023146

Seelan04: Seelan RS, Parthasarathy LK, Parthasarathy RN (2004). "Lithium modulation of the human inositol monophosphatase 2 (IMPA2) promoter." Biochem Biophys Res Commun 324(4);1370-8. PMID: 15504365

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Nov 27, 2014, BIOCYC14A.