Wyo-inositol

A wyo-Inositol, one of the isomers of 1,2,3,4,5,6-hexahydroxycyclohexane, acts as a growth factor in both animals and microorganisms. Draw the most stable chair conformation of myo-inositol. 

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). 

D-Glucose 6-phosphate is converted enzymically into L-wyo-inositol 1-phosphate (20) in a process which requires NAD+. The base-catalysed cyclization of d-xylo-hexos-5-ulose 6-phosphate (21), followed by reduction with borohydride, leads to (20) and epi-inositol 3-phosphate (22) (Scheme 3).59 This has been put forward as a chemical model for the enzymic synthesis. The phosphorylation of inositols with polyphosphoric acid has been described80 and the p-KVs of inositol hexaphosphate have been determined by 31P n.m.r.61... 

In continuation of their studies of the resolution of myo-inositol derivatives via their orthoesters with sugar derivatives, Evstigneeva et al. [296] converted the racemic 1,2 3,4-di-O-cyclohexylidene-wyo-inositol (431) by transesterification with the mannose orthoester (425) into a mixture of diastereoisomers (426) formed by esterification of the 5- and 6-positions of (431). One of the four possible isomers was separated by crystallisation and the other three were obtained by preparative TLC. Partial hydrolysis of the resolved isomers gave both enantiomers of 1,2-0-cyclohexylidene-myo-inositol (432). 

Shvets and co-workers [301] have described a new synthesis of the phosphatidyl-inositol (435) by phosphorylation of the orthoester (437), derived from 2,3 4,5-di-0-cyclohexylidene-L-wyo-inositol, with 1,2-di-O-stearoyl-L-glycerol 3-phosphate in... 

Lorence, A., Chevone, B.I., Mendes, P., and Nessler, C.L., 2004, wyo-Inositol oxygenase offers a possible entry point into plant ascorbate biosynthesis. Plant Physiol. 134 1200-1205. 

Smart, C.C., and Fleming, A.J., 1993, A plant gene with homology to D-wyo-inositol-3-phosphate synthase in rapidly up-regulated during an abscisic-acid-induced morphogenic response in... 

Stieglitz, K.A., Yang, H., Roberts, M.F., and Stec, B., 2005, Reaching for mechanistic consensus across life kingdoms Structure and insight into catalysis of the wyo-inositol-1-phosphate synthase (mIPS) from Archaeoglubus fulgidus. Biochemistry 44 213-224. 

Figure 1. Inositol synthesis and catabolism. Inositol is synthesized from glucose-6-phosphate (Glucose 6-P) by the action of L-wyo-inositol 1-phosphate synthase (MIPS) and wyo-inositol monophosphatase (IMP). IMPase is also required for the last step of inositol (1,4,5)P3 second messenger breakdown. The first step in inositol catabolism utilizes the wyo-inositol oxygenase (MIOX) enzyme, which cleaves the inositol ring to form D-glucuronic acid.

Amer, R.J., Prabhu, K.S., Thompson, J.T., Hildenbrandt, G.R., Liken, A.D., and Reddy, C.C., 2001, wyo-Inositol oxygenase Molecular cloning and expression of a unique enzyme that oxidizes wyo-inositol and D-c/z/ra-inositol. Biochem. J. 360 313-320. 

Figure 3. Biosynthetic pathways from wyo-inositol (Ins) tetrad/,vphosphates to Ins(l,2,3,4,5,6)P6 (InsP6 or phytic acid ) and the pyrophosphate-containing Ins phosphates. The six carbons of the Ins ring are numbered according to the D-numbering convention. Questionmarks indicate synthetic steps that have not been confirmed in chemical, molecular or genetic analyzes. In addition, the tri-phosphate-containing 5-PPP-Ins(l,2,3,4,6)P5 is purely speculative. P = PH204.

Donahue, T.F., and Henry, S.A., 1981, wyo-Inositol-1-phosphate synthase Characteristics of the enzyme and identification of its structural gene in yeast. J. Biol. Chem. 256 7077-7085. 

Tian, F., Migaud, M.E., and Frost, J.W., 1999, Stereochemistry of the wyo-inositol-1-phosphate synthase reaction. J. Biol. Chem. 255 11710-11712. 

Nakanishi, T., Turner, R.J., and Burg, M.B., 1989, Osmoregulatory changes in wyo-inositol transport by renal cells. Proc. Natl. Acad. Sci. USA 86(15) 6002-6006. 

Majumder, A.L., Johnson, M.D., and Henry, S.A., 1997, lL-wyo-inositol-1-phosphate synthase, Biochim. Biophys. Acta, 1348 245-256. 

Whiting, P.H., Palmano, K.P., and Hawthorne, J.N., 1979, Enzymes of wyo-inositol and inositol lipid metabolism in rats with streptozotocin-induced diabetes. Biochem. J. 179 549-553. 

Abu-abied, M., and Holland, D., 1994, The gene cINOl from Citrusparadisi is highly homologous to turl and Inol from the yeast and Spirodela encoding for wyo-inositol 1-phosphate synthase. 

The regioselectivities of /wyo-inositol derivatives towards electrophiles have been studied by using various levels of quantum mechanical calculation. The calculations appear to favour the 0(6) position, but experimentally the 0(3) position is the major site for electrophilic attack. Such experiments usually involve rather polar solvents and repetition of some of the calculations for molecules embedded in a medium of dielectric constant of 40 found 0(3) to be preferred as reaction site. 

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