D- -Myo-inositol 1,4,5-trisphosphate

D-myo-inositol 1,4,5 trisphosphate (I(1,4,5)P3) is a second messenger that liberates Ca2+ from the endoplasmic reticulum via intracellular... 

Bulbring E, T omita T 1969 Effect of calcium, barium and manganese on the action of adrenaline in the smooth muscle of the guinea-pig taenia coli. Proc R Soc Lond B Biol Sci 172 121-136 Marchant JS, Taylor CW 1998 Rapid activation and partial inactivation of inositol trisphosphate receptors by inositol trisphosphate. Biochemistry 37 11524-11533 Somlyo AV, Horiuti K, Trentham DR, Kitazawa T, Somlyo AP 1992 Kinetics of Ca2+ release and contraction induced by photolysis of caged D-myo-inositol 1,4,5-trisphosphate in smooth muscle the effects of heparin, procaine, and adenine nucleotides. J Biol Chem 267 22316-22322... 

Inositol-1,4,5-trisphosphate 5-phosphatase [EC 3.1.3.56], also known as inositol trisphosphate phosphomonoester-ase and inositol polyphosphate 5-phosphatase, catalyzes the hydrolysis of D-myo-inositol 1,4,5-trisphosphate to produce D-myo-inositol 1,4-bisphosphate and orthophosphate. The type I enzyme (but not the type II enzyme) will also hydrolyze inositol 1,3,4,5-tetrakisphosphate at the 5-position. However, neither of the two... 

Wang, X.-L. Akhtar, R.A. Abdel-Latif, A.A. Purification and properties of D-myo-inositol 1,4,5-trisphosphate 3-kinase from bovine iris sphincter smooth muscle effect,s of protein phosphorylation in vitro and in intact muscle. Biochem. J., 308 (Pt 3), 1009-1016 (1995)... 

Communi, D. Vanweyenberg, V. Erneux, C. D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation through a calcium cal-modulin-dependent protein kinase II phosphorylation mechanism. EMBO... 

Optically pure inositol intermediates are very useful for synthesising D-myo-inositol 1,4,5-trisphosphate, which was found to be a second messenger. Ozaki et al [73] studied the resolution of racemic di-O-cylohexylidene-myo-inositol derivatives 17 and 18 by lipase-catalyzed esterification in organic solvents. Lipase from Candida cylindracea exclusively acetylates the hydroxyl group at C-4 or at C-5 of the D-enantiomer of 17 or 18, respectively. Around 100% e.e s of monoacetate products and unreacted starting compounds were obtained. The efficiency of the resolution is affected by the solvent, the most hydrophobic solvents ethyl ether and benzene being more effective than the water miscible solvents such as acetone, THF, and dioxane. 

FIGURE 1 D-myo-lnositol (planar and chair configuration) and D-myo-inositol 1,4,5-trisphosphate [I(1,4,5)P3]. The arrow indicates the site of the ester link with diacylglycerol in phosphatidylinositol. The negative charge of the phosphate groups is not indicated. From Dean and Beaven (1989, Fig. 1, p. 200). 

Neurotransmitters, photons and hormones stimulate receptors on the surface of the target cells causing mobilization of the calcium ion in intracellular stores, thereby triggering physiological responses to occur. The physiological process had been known but it was not clear how the outer information (first messengers), which cannot permeate the cell membrane, was transmitted to the calcium stores. In 1983, this question was resolved by showing experimentally that D-myo-inositol 1, 4, 5-trisphosphate... 

The reaction of 77 with racemic epoxide 78 in the presence of a catalytic amount of HBF4 OEt2 in dichloromethane produces a 1 1 mixture of diastereomeric alcohols (67% yield) that upon separation affords 79 and 80. Further modification of 79 provides D-( — )-myo-inositol 1,4,5-trisphosphate (81) (D-( —)-IP3), while 80 affords L-( + )-wyo-inositol 1,4,5-trisphosphate (82) (l-( + )-IP3) (Scheme 17) [28]. 

The synthesis of D-myo-inositol 1,4,5-trisphosphate (18) (InsP3) from methyl a-i)-glucopyranose (17), via a type 2 Perrier rearrangement, has been reported by Keddie et al. (Scheme 7). Biological evaluation of the synthetic InsPs showed that this compound evoked a selective Ca + release via activation of InsP receptors. 

Cifuentes, ME, Delaney, T and Rebecchi, MJ (1994) D-myo-inositol 1,4,5-trisphosphate inhibits binding of phospholipase C -delta 1 to bUayer membranes. JBiol Chem, 269,1945-1948. 

L-Quebrachitol has served as a chiral source of l-D-3-deoxy-3-fluoro-2,4,5-myo-inositol trisphosphate, l-D-3-deoxy-3-fluoro-l,2,4,5-myo-inositol tetrakis-phosphate and of l-D-l,2,4,5-wyo-inositol tetrakisphosphate. The last two compounds are nearly equipotent to 1-D-myo-inositol 1,4,5 trisphosphate in both binding and Ca. release experiments. ... 

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