Definition: 
   myo-Inositol hexakis(dihydrogen phosphate). Complexing agent for
   removal of traces of heavy metal ions. It acts also as a hypocalcemic
   agent.
   
   Synonyms:
   Inositol Hexaphosphate.
   Phytin.
   
   Phytic Acid Reviews & Editorials
   The role of phytic acid in legumes: antinutrient or beneficial
   function?
   J Physiol Biochem 2000 Sep;56(3):283-94
   Urbano G. Lopez-Jurado M. Aranda P. Vidal-Valverde C. Tenorio E.
   Porres J.
   This review describes the present state of knowledge about phytic acid
   (phytate), which is often present in legume seeds. The antinutritional
   effects of phytic acid primarily relate to the strong chelating
   associated with its six reactive phosphate groups. Its ability to
   complex with proteins and particularly with minerals has been a
   subject of investigation from chemical and nutritional viewpoints. The
   hydrolysis of phytate into inositol and phosphates or phosphoric acid
   occurs as a result of phytase or nonenzymatic cleavage. Enzymes
   capable of hydrolysing phytates are widely distributed in
   micro-organisms, plants and animals. Phytases act in a stepwise manner
   to catalyse the hydrolysis of phytic acid. To reduce or eliminate the
   chelating ability of phytate, dephosphorylation of hexa- and
   penta-phosphate forms is essential since a high degree of
   phosphorylation is necessary to bind minerals. There are several
   methods of decreasing the inhibitory effect of phytic acid on mineral
   absorption (cooking, germination, fermentation, soaking, autolysis).
   Nevertheless, inositol hexaphosphate is receiving increased attention
   owing to its role in cancer prevention and/or therapy and its
   hypocholesterolaemic effect.
   Dietary factors influencing zinc absorption.
   J Nutr 2000 May;130(5S Suppl):1378S-83S
   Lonnerdal B. Urbano G. Lopez-Jurado M. Aranda P. Vidal-Valverde C.
   Tenorio E. Porres J.
   Marginal zinc deficiency and suboptimal zinc status have been
   recognized in many groups of the population in both less developed and
   industrialized countries. Although the cause in some cases may be
   inadequate dietary intake of zinc, inhibitors of zinc absorption are
   most likely the most common causative factor. Phytate, which is
   present in staple foods like cereals, corn and rice, has a strong
   negative effect on zinc absorption from composite meals. Inositol
   hexaphosphates and pentaphosphates are the phytate forms that exert
   these negative effects, whereas the lower phosphates have no or little
   effect on zinc absorption. The removal or reduction of phytate by
   enzyme (phytase) treatment, precipitation methods, germination,
   fermentation or plant breeding/genetic engineering markedly improves
   zinc absorption. Iron can have a negative effect on zinc absorption,
   if given together in a supplement, whereas no effect is observed when
   the same amounts are present in a meal as fortificants. Cadmium, which
   is increasing in the environment, also inhibits zinc absorption. The
   amount of protein in a meal has a positive effect on zinc absorption,
   but individual proteins may act differently; e.g., casein has a modest
   inhibitory effect of zinc absorption compared with other protein
   sources. Amino acids, such as histidine and methionine, and other
   low-molecular-weight ions, such as EDTA and organic acids (e.g.,
   citrate), are known to have a positive effect on zinc absorption and
   have been used for zinc supplements. Knowledge about dietary factors
   that inhibit zinc absorption and about ways to overcome or remove
   these factors is essential when designing strategies to improve the
   zinc nutrition of vulnerable groups.
   Inositol hexakisphosphate and beta-cell stimulus-secretion coupling.
   Anticancer Res 1999 Sep-Oct;19(5A):3737-41
   Barker CJ. Berggren PO. Lonnerdal B. Urbano G. Lopez-Jurado M. Aranda
   P. Vidal-Valverde C. Tenorio E. Porres J.
   Inositol hexakisphosphate (InsP6) inhibits serine/threonine protein
   phosphatases type-1 (PP1), type-2A (PP2A) and type-3 (PP3) in a
   concentration-dependent manner. Since the activity of voltage-gated L-
   type Ca(2+)-channels is increased by inhibition of serine/threonine
   protein phosphatases, this may explain trhe increased Ca(2+)-channel
   activity obtained in the presence of InsP6. In insulin-secreting
   cells, InsP6 is therefore likely to be one of the key elements
   modulating Ca(2+)-influx over the plasma membrane. InsP6 can also
   modulate insulin exocytosis in permeabilized cells. Concentrations of
   InsP6 above 20 microM stimulated insulin secretion at basal
   Ca(2+)-concentration (30 nM) and primed Ca(2+)-induced exocytosis (10
   microM), both effects being due to activation of PKC. Hence, InsP6 can
   play an important modulatory role in the regulation of insulin
   exocytosis and the specific role may then be to recruit secretory
   granules to the site of exocytosis. The fact that some InsP6 is
   localised to membranes, so being topographically disposed to regulate
   ion channels as well as exocytosis, and that it has a rapid rate of
   turnover in glucose- stimulated insulin-secreting cells, suggest novel
   functions for InsP6 in the insulin secretory process.
   Metabolism and cellular functions of IP6: a review.
   Anticancer Res 1999 Sep-Oct;19(5A):3733-6
   Shamsuddin AM. Barker CJ. Berggren PO. Lonnerdal B. Urbano G.
   Lopez-Jurado M. Aranda P. Vidal-Valverde C. Tenorio E. Porres J.
   Inositol hexaphosphate (IP6) has a demonstrably effective anti-cancer
   action against a variety of experimental tumors. However, the
   mechanisms of its actions are yet to be completely discerned. Studies
   in my laboratory have shown that IP6 is rather rapidly absorbed by
   rats in vivo. Ion exchange chromatography demonstrates the presence of
   inositol and IP1-6 in gastric epithelial cells as early as within 1 h
   of intragastric 3H-IP6 administration. The metabolized IP6, in the
   form of inositol and IP1 is transported via plasma and reaches distant
   organs as well as tumors. In rats, the urinary metabolites of IP6 are
   inositol and IP1. However, in humans 1-3% of total administered IP6 is
   excreted in the urine as IP6; the level shows a normal oscillation
   between 0.5-6 mg/L [F. Grases et al]. Investigations of the uptake and
   metabolism by a variety of cancer cell lines in vitro also demonstrate
   an instantaneous absorption of IP6. The rate and pattern at which IP6
   is metabolized by cancer cells varies depending on the cell type.
   Intracellular inositols accumulated mostly (80-97%) in the cytosol as
   inositol and IP1-6. IP6 treatment of all the cell lines tested so far
   demonstrates that it is cytostatic and not cytotoxic. Along with
   inhibition of cell proliferation, there is enhanced differentiation of
   malignant cells to a more mature phenotype, often resulting in
   reversion to normal. Studies of the expression of tumor suppressor
   gene demonstrate up-regulation of wild type p53 and down-regulation of
   the mutant form. Since p53-mediated cell cycle arrest may be the
   direct result of induction of WAF-1 gene (p21WAF-1/CIP1), our studies
   demonstrate that IP6 up-regulates the expression of p21WAF-1/CIP1 in a
   dose-dependent manner. These data strongly point towards the
   involvement of signal transduction pathways, cell cycle regulatory
   genes, differentiation genes, oncogenes and perhaps, tumor suppressor
   genes in bringing about the observed anti-neoplastic action of IP6.
   Phytate (IP6) is a powerful agent for preventing calcifications in
   biological fluids: usefulness in renal lithiasis treatment.
   Anticancer Res 1999 Sep-Oct;19(5A):3717-22
   Grases F. Costa-Bauza A. Shamsuddin AM. Barker CJ. Berggren PO.
   Lonnerdal B. Urbano G. Lopez-Jurado M. Aranda P. Vidal-Valverde C.
   Tenorio E. Porres J.
   The extraordinary capacity of phytate (myo-inositol hexaphosphate), a
   substance present in blood, urine, interstitial and intracellular
   fluids, to inhibit crystallization of calcium salts (oxalate and
   phosphate) is discussed. Its role in preven (HOME) ting calcium renal stone
   formation is specifically presented and discussed. "In vitro" and "in
   vivo" experiments, as well as clinical studies clearly demonstrated
   that phytate plays an important role as a crystallization inhibitor of
   calcium salts in biological fluids and becomes a clear alternative in
   the treatment of calcium oxalate renal lithiasis.
   


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