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MetaCyc Pathway: 1D-myo-inositol hexakisphosphate biosynthesis III (Spirodela polyrrhiza)
Inferred from experiment

Enzyme View:

Pathway diagram: 1D-myo-inositol hexakisphosphate biosynthesis III (Spirodela polyrrhiza)

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.

Synonyms: lipid-independent phytic acid biosynthesis, lipid-independent InsP6 biosynthesis, lipid-independent phytate biosynthesis, hexakisphosphate biosynthesis (lipid-independent), phytate biosynthesis

Superclasses: BiosynthesisSecondary Metabolites BiosynthesisSugar Derivatives BiosynthesisCyclitols BiosynthesisPhytate Biosynthesis

Some taxa known to possess this pathway include : Spirodela polyrhiza, Zea mays

Expected Taxonomic Range: Viridiplantae

General Background

phytate (phytate, phytic acid) is one of the most prevalent forms of phosphorylated inositols in the eukaryotic cell, with a total concentration of 15-100 μM [Szwergold87, French91, Bunce93]. It's cellular distribution is not completely known - some of it is soluble, some is "wall-papered" around membranes, while some is bound to proteins [Shears98]. In plant seeds, large amount of phytate are complexed with cations and deposited as globular inclusions in membrane-bound storage bodies [Coelho05].

The compound has been proposed to have a number of signaling roles, including regulation of insulin exocytosis [Efanov97], regulation of nuclear mRNA export [York99, Saiardi00a], binding of the clathrin assembly proteins AP2 and AP3 [Theibert91, Chadwick92], inhibition of clathrin cage assembly [Norris95, Ye95], and inhibition of serine and threonine protein phosphatases that are thought to regulate L-type Ca2+ channels [Larsson97].

Phytate in Plants

In plant cells phytate serves as a storage form of myo-inositol, phosphate and mineral nutrients for utilization during seed germination and seedling growth. It is deposited within single-membrane storage organelles referred to as protein bodies and is usually present as mixed complexes with different cations, including K+, Mg2+, Ca2+, Fe2+, and Zn2+, known as phytin [Raboy01, Raboy96]. Although phytin only makes up about 1% of the seed weight, it may contain up to 80% of the total seed phosphorus [Coelho05]. Phytate is also present in other plant tissues and organs such as pollen, roots, tuber and turions in smaller quantities [Raboy03].

About This Pathway

Most of our knowledge about phytate biosynthesis concerns lipid-dependent pathways, where the inositol phosphate precursor originates from a phospholipid, as described in pathways 1D-myo-inositol hexakisphosphate biosynthesis I (from Ins(1,4,5)P3) and 1D-myo-inositol hexakisphosphate biosynthesis II (mammalian). However, information exists that suggests that certain organisms synthesize this compound from myo-inositol or 1D-myo-inositol 3-monophosphate that do not originate from phospholipids.

To date such pathways have only been reported in two organisms - the aquatic monocotyledonous plant Spirodela polyrhiza [Brearley96a] (described here), and the slime mold Dictyostelium discoideum, which utilizes different intermediates [Stephens90] (see 1D-myo-inositol hexakisphosphate biosynthesis IV (Dictyostelium)). The sequence of conversions from 1D-myo-inositol 3-monophosphate to phytate in Spirodela polyrhiza has been illucidated only by the use of radiolabeled compounds and no enzymes have been characterized from this organism. However, the pathway is also believed to exist in maize, and several maize enzymes have been characterized [Shukla04, Shi03, Shi05c].

These include myo-inositol-3-monophosphate synthase (MIPS) [Shukla04], which produces 1D-myo-inositol 3-monophosphate from D-glucopyranose 6-phosphate, and myo-inositol kinase [Shi05c], which which produces 1D-myo-inositol 3-monophosphate from myo-inositol.

The rest of the enzymes of this pathway have not been characterized in great detail as yet. While a myo-inositol polyphosphate kinase that phosphorylates D-myo-inositol (3,4,5,6)-tetrakisphosphate has been detected in maize, the exact nature of the kinase activity of this enzyme is not yet known as the reaction product have not been characterized [Shi03].

Variants: 1D-myo-inositol hexakisphosphate biosynthesis I (from Ins(1,4,5)P3), 1D-myo-inositol hexakisphosphate biosynthesis II (mammalian), 1D-myo-inositol hexakisphosphate biosynthesis IV (Dictyostelium), 1D-myo-inositol hexakisphosphate biosynthesis V (from Ins(1,3,4)P3), superpathway of 1D-myo-inositol hexakisphosphate biosynthesis (plants)

Created 07-Sep-2005 by Tissier C, TAIR


Brearley96: Brearley CA, Hanke DE (1996). "Inositol phosphates in the duckweed Spirodela polyrhiza L." Biochem J 314 ( Pt 1);215-25. PMID: 8660286

Brearley96a: Brearley CA, Hanke DE (1996). "Metabolic evidence for the order of addition of individual phosphate esters in the myo-inositol moiety of inositol hexakisphosphate in the duckweed Spirodela polyrhiza L." Biochem J 314 ( Pt 1);227-33. PMID: 8660287

Bunce93: Bunce CM, French PJ, Allen P, Mountford JC, Moor B, Greaves MF, Michell RH, Brown G (1993). "Comparison of the levels of inositol metabolites in transformed haemopoietic cells and their normal counterparts." Biochem J 289 ( Pt 3);667-73. PMID: 8435066

Chadwick92: Chadwick CC, Timerman AP, Saito A, Mayrleitner M, Schindler H, Fleischer S (1992). "Structural and functional characterization of an inositol polyphosphate receptor from cerebellum." J Biol Chem 267(5);3473-81. PMID: 1371119

Coelho05: Coelho CM, Tsai SM, Vitorello VA (2005). "Dynamics of inositol phosphate pools (tris-, tetrakis- and pentakisphosphate) in relation to the rate of phytate synthesis during seed development in common bean (Phaseolus vulgaris)." J Plant Physiol 162(1);1-9. PMID: 15700415

Efanov97: Efanov AM, Zaitsev SV, Berggren PO (1997). "Inositol hexakisphosphate stimulates non-Ca2+-mediated and primes Ca2+-mediated exocytosis of insulin by activation of protein kinase C." Proc Natl Acad Sci U S A 94(9);4435-9. PMID: 9114007

French91: French PJ, Bunce CM, Stephens LR, Lord JM, McConnell FM, Brown G, Creba JA, Michell RH (1991). "Changes in the levels of inositol lipids and phosphates during the differentiation of HL60 promyelocytic cells towards neutrophils or monocytes." Proc Biol Sci 245(1314);193-201. PMID: 1684044

Larsson97: Larsson O, Barker CJ, Sjoholm A, Carlqvist H, Michell RH, Bertorello A, Nilsson T, Honkanen RE, Mayr GW, Zwiller J, Berggren PO (1997). "Inhibition of phosphatases and increased Ca2+ channel activity by inositol hexakisphosphate." Science 278(5337);471-4. PMID: 9334307

Norris95: Norris FA, Ungewickell E, Majerus PW (1995). "Inositol hexakisphosphate binds to clathrin assembly protein 3 (AP-3/AP180) and inhibits clathrin cage assembly in vitro." J Biol Chem 270(1);214-7. PMID: 7814377

Raboy01: Raboy V (2001). "Seeds for a better future: 'low phytate' grains help to overcome malnutrition and reduce pollution." Trends Plant Sci 6(10);458-62. PMID: 11590064

Raboy03: Raboy V (2003). "myo-Inositol-1,2,3,4,5,6-hexakisphosphate." Phytochemistry 64(6);1033-43. PMID: 14568069

Raboy96: Raboy V, Gerbasi P (1996). "Genetics of myo-inositol phosphate synthesis and accumulation." Subcell Biochem 26;257-85. PMID: 8744268

Saiardi00a: Saiardi A, Caffrey JJ, Snyder SH, Shears SB (2000). "Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae." FEBS Lett 468(1);28-32. PMID: 10683435

Shears98: Shears SB (1998). "The versatility of inositol phosphates as cellular signals." Biochim Biophys Acta 1436(1-2);49-67. PMID: 9838040

Shi03: Shi J, Wang H, Wu Y, Hazebroek J, Meeley RB, Ertl DS (2003). "The maize low-phytic acid mutant lpa2 is caused by mutation in an inositol phosphate kinase gene." Plant Physiol 131(2);507-15. PMID: 12586875

Shi05c: Shi J, Wang H, Hazebroek J, Ertl DS, Harp T (2005). "The maize low-phytic acid 3 encodes a myo-inositol kinase that plays a role in phytic acid biosynthesis in developing seeds." Plant J 42(5);708-19. PMID: 15918884

Shukla04: Shukla S, VanToai TT, Pratt RC (2004). "Expression and nucleotide sequence of an INS (3) P1 synthase gene associated with low-phytate kernels in maize (Zea mays L.)." J Agric Food Chem 52(14);4565-70. PMID: 15237968

Stephens90: Stephens LR, Irvine RF (1990). "Stepwise phosphorylation of myo-inositol leading to myo-inositol hexakisphosphate in Dictyostelium." Nature 346(6284);580-3. PMID: 2198472

StevensonPaulik05: Stevenson-Paulik J, Bastidas RJ, Chiou ST, Frye RA, York JD (2005). "Generation of phytate-free seeds in Arabidopsis through disruption of inositol polyphosphate kinases." Proc Natl Acad Sci U S A 102(35);12612-7. PMID: 16107538

Szwergold87: Szwergold BS, Graham RA, Brown TR (1987). "Observation of inositol pentakis- and hexakis-phosphates in mammalian tissues by 31P NMR." Biochem Biophys Res Commun 149(3);874-81. PMID: 3426614

Theibert91: Theibert AB, Estevez VA, Ferris CD, Danoff SK, Barrow RK, Prestwich GD, Snyder SH (1991). "Inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate receptor proteins: isolation and characterization from rat brain." Proc Natl Acad Sci U S A 88(8);3165-9. PMID: 1849645

Ye95: Ye W, Ali N, Bembenek ME, Shears SB, Lafer EM (1995). "Inhibition of clathrin assembly by high affinity binding of specific inositol polyphosphates to the synapse-specific clathrin assembly protein AP-3." J Biol Chem 270(4);1564-8. PMID: 7829485

York99: York JD, Odom AR, Murphy R, Ives EB, Wente SR (1999). "A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export." Science 285(5424);96-100. PMID: 10390371

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

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

Chen00b: 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

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

Ives00: Ives EB, Nichols J, Wente SR, York JD (2000). "Biochemical and functional characterization of inositol 1,3,4,5, 6-pentakisphosphate 2-kinases." J Biol Chem 275(47);36575-83. PMID: 10960485

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

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

Phillippy94: Phillippy BQ, Ullah AH, Ehrlich KC (1994). "Purification and some properties of inositol 1,3,4,5,6-Pentakisphosphate 2-kinase from immature soybean seeds." J Biol Chem 269(45);28393-9. PMID: 7961779

Stephens90a: Stephens LR, Kay RR, Irvine RF (1990). "A myo-inositol D-3 hydroxykinase activity in Dictyostelium." Biochem J 272(1);201-10. PMID: 2176081

Verbsky02: Verbsky JW, Wilson MP, Kisseleva MV, Majerus PW, Wente SR (2002). "The synthesis of inositol hexakisphosphate. Characterization of human inositol 1,3,4,5,6-pentakisphosphate 2-kinase." J Biol Chem 277(35);31857-62. PMID: 12084730

Xie96: Xie W, Kaetzel MA, Bruzik KS, Dedman JR, Shears SB, Nelson DJ (1996). "Inositol 3,4,5,6-tetrakisphosphate inhibits the calmodulin-dependent protein kinase II-activated chloride conductance in T84 colonic epithelial cells." J Biol Chem 271(24);14092-7. PMID: 8662902

Yang00: Yang X, Shears SB (2000). "Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase." Biochem J 351 Pt 3;551-5. PMID: 11042108

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
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