Myo-Inositol 1,3,4-trisphosphate

This enzyme [EC 2.7.1.133], also referred to as lo-myo-inositol-trisphosphate 6-kinase, catalyzes the reaction of ATP with iD-myo-inositol 1,3,4-trisphosphate to produce ADP and iD-myo-inositol 1,3,4,6-tetrakisphos-phate. 

Shears, S.B. The pathway of myo-inositol 1,3,4-trisphosphate phosphorylation in liver. Identification of myo-inositol 1,3,4-trisphosphate 6-kinase, myo-inositol 1,3,4-trisphosphate 5-kinase, and myo-inositol 1,3,4,6-tetrakisphosphate 5-kinase. J. Biol. Chem., 264, 19879-19886 (1989)... 

Also known as inositol-1,4-bisphosphate 1-phosphatase [EC 3.1.3.57], this enzyme catalyzes the hydrolysis of d-myo-inositol 1,4-bisphosphate to generate D-myo-inositol 4-phosphate and orthophosphate. This enzyme can also act on inositol 1,3,4-trisphosphate (forming inositol 3,4-bisphosphate). Inositol-1,4,5-trisphosphate 1-phos-... 

S ATP -I- D-myo-inositol 3,4,5,6-tetrakisphosphate <1-3, 5, 6, 7> (<1,2> i.e. L-myo-inositol 1,4,5,6-tetrakisphosphate, phosphorylation site l-3 or d-1 substitution position [2] <1,2> no activity with D-myo-inositol 1,3,4,5-tetrakisphosphate [2] <5> no activity with inositol-l,3,4,5-tetrakisphos-phate [6] <7> enzyme has both inositol-3,4,5,6-tetrakisphosphate 1-ki-nase and inositol-l,3,4-trisphosphate 5/6 kinase activity, 2 times higher activity than with inositol-1,3,4-trisphosphate, no activity with inositol-... 

Figure 1. Schematic representation of the brain inositol signaling system. The quantities of IMPase isoenzymes and IPPase are increased by chronic lithium treatment occurring at either the gene or protein levels. Inositol in this diagram indicates the myo-inositol isomer. Calbindin -calcium binding protein DAG- diacyl glycerol Gq-GTP binding protein IMPase 1 — inositol mono phosphatase 1 IPPase- inositol polyphosphate 1-phosphatase Ins(l)P, Ins(3)P, Ins(4)P-inos-itol monophosphates Ins(l,3)P2 - inositol 1,3-bisphosphate Ins( 1,4)/ 2 - inositol 1,4-bisphos-phate Ins(3,4)/)2- inositol 3,4-bisphosphate Ins (1,4,5)P3 - inositol 1,4,5-trisphosphate Ins( 1,3,4)/ 3 - inositol 1,3,4-trisphosphate Li+-lithium PA - phosphatidic acid PI- phosphatidyl inositol PIP- phosphatidyl inositol 4-phosphate PIP2- phosphatidyl inositol 4,5-bisphosphate PIP3- phosphatidyl inositol 3,4,5 trisphosphate PLC - phospholipase-C, VPA-valproate.

The synthesis by established routes of racemic myo-inositol 1,4,6-trisphosphor-othioate and myo-inositol 1,3,4-trisphosphorothioate as low intrinsic partial agonists at the platelet wyo-inositol 1,4,5-trisphosphate receptor have been reported. ... 

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... 

Strict adherence to the lowest-locant rule sometimes obscures straightforward metabolic relationships. For example, consider the dephosphorylation of (22) - (23) (Figure 5). The IUPAC (1976) rules require that compound (22) be labeled lD-myo-inositol-l,3,4,5-tetrakisphosphate rather than lL-myo-inositol-l,3,5,6-tetrakisphosphate, so that substituents are attached to carbons with lower numbers, whereas (23) should be labeled lL-myo-inositol-1,5,6-trisphosphate rather than lD-myo-inositol-3,4,5-trisphos-phate. Thus, to describe the dephosphorylation reaction (Figure 5), the necessity to switch between D and L numbering leads to the following statement ... 

Syntheses of ( ) myo-inositol 1,2-bisphosphate and myo-inositol 1,2,3-trispho-sphate by phosphorylation of ( ) 3,4,5,6-tetra-O-benzyl-myo-inositol and 4,5,6-tri-O-benzoyl-myo-inositol, respectively, using dibenzyl AT.iV -diisopropylpho-sphoramidite then oxidation have been reported, and d- and L-myo-inositol 1,4,6-trisphosphate has been made from a myo-inositol derivative and resolved with (5)-(+)-0-acetylmandelic acid to obtain the required pure enantiomers. Full details of an earlier report (see Vol. 27, p. 222, ref. 146) on the syntheses of L-Jcy//o-inositol 1,2,4-trisphosphate, scyllo-inositol 1,2,4,5-tetrakis-phosphate and -phosphorothioate and 2-deoxy-2-fluoro-D,L-myo-inositol have been reported. ... 

Phytic acid (wyo-inositol hexaphosphate) can be desymmetrized using phopha-tases found in Bakers yeast which allows the isolation of D-myo-inositol 1,2,6-trisphosphate. This was further used to prepare 3,4,5-tri-O-phenylcarbamoyl d-wyo-inositol. ... 

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... 

In relation to the substitution reaction of the 1,2-ketal 47, the reaction of 1,2-dibutyroyl inositol 72 with 1.1 equiv of butyric anhydride in pyridine was found to give predominantly the 3-0-acylation product 73 in 50% yield together with smaller amounts of 74 and 75. 0 One product 74 was used to prepare racemic 2,3,6-tri-O-butyroyl-myo-inositol 1,4,5-trisphosphate, which was proved to be a membrane-permeant Ins(l,4,5)P3 agonist (Scheme 3-8). 

The triethylsilyl ether 147 thus formed regiospecifically from the diol 150 [Rl=(BnO)2 (0), R2=Bn], which was optically resolved by a chiral column chromatography, was transformed to Ins(2,4,5)P3 and Ins(l,4,5)P3 (Schema 3-23). At this stage, temporary protection of OH-1 with the silyl group is not necessary, i.e. 150 can be directly phosphorylated by the phosphite-phosphonium approach as described in the section on phosphorylation (Scheme 2-6). H The diol 150 was used furthermore as a versatile synthetic intermediate for the synthesis of myo-inositol 1,2-cyclic-4,5-trisphosphate 152 (Scheme 3-23), 8 2-acyl analogues of Ins(1,4,5)P3, and inositol phospholipid. 

---