Inositol hexaphosphate

FIGURE 15.38 The structures of inositol pentaphosphate and inositol hexaphosphate, the functional analogs of BPG in birds and reptiles. 

Myo-inositol is one of the most biologically active forms of inositol. It exists in several isomeric forms, the most common being the constituent of phospholipids in biological cell membranes. It also occurs as free inositol and as inositol hexaphosphate (IP6) also known as phytate which is a major source from food. Rice bran is one of the richest sources of IP6 as well as free inositol. Inositol is considered to belong to the B-complex vitamins. It is released in the gastrointestinal tract of humans and animals by the dephosphorylation of IP6 (phytate) by the intestinal enzyme phytase. Phytase also releases intermediate products as inositol triphosphate and inositol pentaphosphate. Inositol triphosphate in cellular membrane functions as an important intra- and intercellular messenger, that merits its value as a nutritional therapy for cancer. 

HUANG c MA w Y, HECHT s s, DONG z (1997) Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3 kinase. [pubhshed erratum appears in Cancer Res (1997) 57(22) 5198] Cancer Res, 57 2873-8. 

JARIWALLA R (1999) Inositol hexaphosphate (IP6) as an anti-neoplastic and lipid lowering agent. Anticancer Research, 19 3699-702. 

G. R. Findenegg and J. A. Nelenians, The effect of phytase on the availability of P from myo-inositol hexaphosphate (phytate) for maize root. Plant Soil 754 189 (1993). 

The growth of ectomycorrhizal trees is frequently improved by their increased phosphorus (P) accumulation (3), and this, in turn, is related to the intensity of the mycorrhizal infection. Ectomycorrhizal fungi solubilize insoluble forms of A1 and Ca phosphates as well as inositol hexaphosphates, though a wide interstrain variability has been recorded (112). These complex P forms are digested by the secretion of extracellular acid and alkaline phosphomono- and phosphodi-ester-ases. Pi in soil solutions is easily taken up by ectomycorrhizal hyphae and then translocated to the host roots. Its absorption and efflux are probably regulated... 

Phytate (myo-inositol hexaphosphate Fig. 15.3, structure 33) is found in many food species and can be considered as a phytochemical. Its role in the plant is primarily as a phosphate store in seeds, but it is found in other tissues as well, for example, tubers (Harland et al., 2004). Phytate and its hydrolysis products are anti-nutrients that chelate metal ions and thus reduce their bioavailability (Persson et al., 1998 House, 1999). This is particularly a problem with cereal grains, but pre-processing can improve mineral absorption from these foods (Agte and Joshi, 1997). There is some concern that high phytate foods could also contain higher levels of toxic heavy metals caused by natural accumulation. Plants also contain phytate-degrading enzymes that can also influence metal ion bioavailability (Viveros et al., 2000). 

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... 

Goodford PI, St-Louis J, Wootton R. A quantitative analysis of the effects of 2,3-diphosphoglycerate, adenosine triphosphate and inositol hexaphosphate on the oxygen dissociation curve of human haemoglobin. J Physiol 1978 283 397. 

We next turn to the effect of adding D-2,3-bisphosphoglycerate (BPG, previously known as DPG) and inositol hexaphosphate (IHP). 

The free iron in the food enters the intestinal mucus from which it is absorbed by the epithelial cells via a transporter protein. This absorption is decreased by tea, coffee and phytate (inositol hexaphosphate) present in cereal fibre. Iron combined in haem is absorbed directly by epithehal cells after being released from haem-containing protein. The free iron is released in these cells by the enzyme haem oxidase. The free Fe is then bound to paraferritin and released into the blood where it is bound by ferritin. The three reactions are as follows. 

This enzyme [EC 3.1.3.26], also known as phytase, phy-tate 6-phosphatase, and myo-inositol-hexaphosphate 6-phosphohydrolase, catalyzes the hydrolysis of myoinositol hexakisphosphate to produce 1-myo-inositol... 

Vucenik I, et al. Novel anticancer function of inositol hexaphosphate inhibition of human rhabdomyosarcoma in vitro and in vivo. Anticancer Res 1998 18(3A) 1377-1384. 

Hydrolysis of mt/o-inositol l(3),2-cyclic phosphate under acidic or alkaline conditions affords a mixture of myo-inositol l(3)-phosphate and myo-inositol 2-phosphate, with the former preponderating.275 As the cyclic phosphate may be prepared275 from the 2-phosphate, which is itself readily obtained from myo-inositol hexaphosphate by enzymic cleavage,268,276 and as the l(3)-phosphate may be isolated277 from the hydrolysis mixture, the reaction sequence provides a convenient way... 

Some are inhibited by ATP 173 l7 lb and others by eicosanoids475 or inositol hexaphosphate.476 Some of the ATP-sensitive channels contain an ABC transporter subunit and are binding sites for sulfonylureas and other drugs. See discussion on p. 421. A number of human disorders in Kir channels have been identified.468 Tire human Kir channels participate in regulation of resting membrane potentials in K+ homeostasis, control of heart rate, and hormone secretion.468 A third group of K+ channels are dimeric, but each subunit contains two tandem P regions and 4-8 transmembrane helices.455... 

Figure 6.6 Spectrophotometric titration of the binding of inositol hexaphosphate (IHP) to methemoglobin (Methb). The complex has an increased absorbance at 512 and 649 nm, and no increases at 640,618,588, and 599 ran. The concentration of methemoglobin (20 fjM) is about 14 times higher than the dissociation constant of 1.4 f.iM for the complex. The intersection of the slope of the increase in absorbance with the maximum value gives the stoichiometry (1, in this case). Note that this simple procedure cannot be used if the protein is not initially present at such a high concentration relative to the dissociation constant, since the assumption is that all the added ligand is bound to the protein for the early additions.

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