Myoinositol phosphate

Figure 5. Hydrolysis of myoinositol phosphates - alternative numbering.

Shears, S.B., 1996, Inositol pentakis- and hexakisphosphate metabolism adds versatility to the actions of inositol polyphosphates novel effects on ion channels and protein traffic. In myoinositol phosphates, phosphoinositides, and signal transduction. Subcell. Biochem., Vol. 26, Plenum Press, N.Y., Chapt. 7, pp. 187-226. 

Dubreuil, D., Cleophax, J., De Almeida, M. V., Verre-Sebrie, C., Liaigre, J., Vass, G., Gero, S. D. Stereoselective synthesis of 6-deoxy and 3,6-dideoxy-D-myoinositol precursors of deoxy myoinositol phosphate analogs from D-galactose. Tetrahedron 1997, 53,16747-16766. Paquette, L. A., Kinney, M. J., Dullweber, U. Practical Synthesis of Spirocyclic Bis-C,C-glycosides. Mechanistic Models in Explanation of Rearrangement Stereoselectivity and the Bifurcation of Reaction Pathways. J. Org. Chem. 1997, 62,1713-1722. 

Considerable research effort has been focused on the preparation of compounds of biochemical interest, using electrophilic reactions of phosphoramidites and phosphorochloridites to prepare modified phosphates of nucleosides or lipids. Intense interest has been shown in the synthesis of myoinositol phosphates, and also of aminoalkylphosphonic acids and their derivatives and analogues. Away from the biological emphasis, however, the first (recorded) syntheses of acetylenic phosphates have been described, and so have the first 1-alkoxyphosphole, the first cis amino-iminophosphine, and the first dithiaphospholium ions ex Phosphorus semper aliquid novi The use of silyl phosphites for synthetic purposes seems to be an increasing trend, while the number of papers on metaphosphate seems to be in decline. 

Problems with phosphorylation In the preparation of myoinositol phosphates and related compounds, the most crucial problem to be solved is the multiple phosphorylation of polyol derivatives. Especially vicinal diols 4 are very difficult to be transformed to the diphosphates 7, mainly because the monophosphorylation product 5 is prone to cyclization to the 5-membered cyclic phosphate 6 rather than undergoing the second phosphorylation (Scheme 1-5). These facts stimulated efforts to develop a new phosphorylation methodology, and in 1987 two types of new phosphorylation methods employing P(III) and P(IV) reagents were successfully introduced for the synthesis of Ins(l,4,5)P3 and Ins(1,3,4,5)P4. 

Figure 2 Phosphodiesteratic cleavage (phospholipase C) of phospha-tldvllnositol-4.5-bisphosphate. Phosphatidylinositol and phosphatidylinositol-4-monophosphate are also hydrolyzed in a similar manner yielding 1,2-diacylglycerol and the corresponding myoinositol phosphates such as myoinositol-1-monophosphate (plus myoinositol-1,2-cyclic phosphate) and myoinositol-4-roonophosphate. P indicates phosphate groups.

Barrientos L.G., Murthy P.P.N. Conformational studies of myoinositol phosphates. Carbohydrate Research, 296 39-54 (1996). 

Myoinositol bis(trichloroethyl)phosphates were not as stable to pyridine at 20°, as were the related benzyl analogs. ... 

A. Inositol Phosphates.—Phosphatidyl inositol (71) is hydrolysed in mammalian tissues to wyo-inositol 1,2-cyclic phosphate (72).i myoinositol 1-phosphate (73) is released simultaneously but is not converted into (72) by the enzyme system. Periodate oxidation of (73) liberates orthophosphate quantitatively, the unstable dialdehyde phosphate (74) being an intermediate. Little or no orthophosphate is released from glucose 6-phosphate under the same oxidative conditions, and this reaction has been used to assay (73). 

Miller has reported a minimal kinase for the phosphorylative enantioselective desymmetrization of a meio-inositol derivative. Peptide 132, identihed from a small library, provided the highest selectivity using the meso-tno 130 as substrate. This approach was applied to a hve-step synthesis of D-myoinositol-1-phosphate from readily available myoinositol ... 

This enzyme [EC 3.1.3.25], also referred to as myo-inosi-tol-l(or 4)-monophosphatase and myo-inositol-l-phos-phatase, catalyzes the hydrolysis of myo-inositol 1-monophosphate to generate myo-inositol and orthophosphate. Both enantiomers of myo-inositol 1-phosphate and myoinositol 4-phosphate can act as substrates. However, the enzyme does not hydrolyze inositol bisphosphates, tris-phosphates, or tetrakisphosphates. 

Ciulla, R.A., S. Burggraf, K.O. Stetter, and M.F. Roberts (1994). Occurrence and role of di-/Myoinositol-1-1 -phosphate in Methanococcus igneus. Appl. Environ. Microbiol. 60 3660-3664. 

Although the two halves of myoinositol are stereochemically nonequivalent, they are chemically equivalent to an achiral molecule or reagent. In other words, an achiral molecule or reagent does not show preferential selectivity for either side and therefore reacts with both halves at the same rate. However, the biochemical consequence of enantiotopic carbons of most relevance to biochemists is that a chiral molecule, such as an enzyme, can readily distinguish between C-l and C-3 as well as C-4 and C-6 and preferentially reacts with one enantiotopic carbon or another. For example, myo-inositol kinase phosphory-lates myoinositol exclusively at the D-3 position and yields the chiral product, 1 D-myo-inositol-3-monophosphate (15) (Deitz and Albersheim, 1965 Loewus et al., 1982). This is the same isomer produced from glucose-6-phosphate by myo-inositolphosphate synthase (reviewed in Loewus, 1990a). The only route... 

Hegeman, C.E., Good, L.L., and Grabau, E.A., 2001, Expression of D-myoinositol-3-phosphate synthase in soybean. Implications for phytic acid biosynthesis. Plant Physiol. 125 1941-1948. 

Dean-Johnson, M., and Wang, X., 1996, Differentially expressed forms of lL-myoinositol-1-phosphate synthase in Phaseolus vulgaris. J. Biol. Chem. 271 17215-17218. 

Loewus, M.W., and Loewus, F.A., 1980, The C-5 hydrogen isotope-effect in myo-inositol 1-phosphate synthase as evidence for the myoinositol oxidation-pathway. Carbohydr. Res. 82 333-342. 

Inositol is synthesized by the same route in all cells. D-Glucose-6-phosphate (d-G-6-P) is converted to L-mvo-inositol-1 -phosphate (l-I- 1 -P), which can also be termed D-myo-inositol-3-phosphate. The L-I-l-P is then hydrolyzed to myoinositol by a relatively specific phosphatase. As we will see, enzymes that do these reactions in bacteria and archaea can have quite different characteristics from the eukaryotic enzymes. 

Barnett, J.E.G., Rasheed, A., and Corina, D.L., 1973b, Partial reactions of D-glucose 6-phosphate-11-myoinositol 1-phosphate cyclase. Biochem. J. 131 21-30. 

Chen, C.H.J., and Eisenberg, F., 1975, Myoinosose-2 1-phosphate - intermediate in myoinositol 1-phosphate synthase reaction. J. Biol. Chem. 250 2963-2967. 

Eisenberg, F., Jr., 1967, D-myoinositol 1-phosphate as product of cyclization of glucose 6-phosphate and substrate for a specific phosphatase in rat testis. J. Biol. Chem. 242 1375-1382. 

Migaud, M.E., and Frost, J.W., 1996, Elaboration of a general strategy for inhibition of myoinositol 1-phosphate synthase Active site interactions of analogues possessing oxidized reaction centers. J.Am. Chem. Soc. 118 495-501. 

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