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). 

Ubiquitous in seeds is phytic acid, the hexaphosphate ester of inositol, which has been isolated from cucurbit seeds (57). Small amounts of free sugars and terpenoid glycosides (cucurbitacins) are also present (58-60), but starch is absent (1, 1). Cellulosic cell wall materials comprise the remaining carbohydrate content. 

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... 

High-molecular polyphosphates are practically stable in aqueous solution at room temperature and a pH near the neutral point. At 60°C the half-life is about 50 days but it decreases rapidly with rising temperature. The hydrolysis constant of the high-molecular phosphates at 60°C and pH 8 has the value K = 0.9 X 10 and is about a power of ten smaller than that of octaphosphate and roughly equal to that of hexaphosphate (see Fig. 7). 

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. 

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