ABSTRACT
Introduction 398
Inositol Compounds in Cellular Signaling 399
IP3 and Its Receptor 399
IP6 and Its Receptor 400
IP6 as a Signal Molecule 400
In Mammalian Cells 400
Signal Transduction by IP3 and IP6 Along the Evolutionary Tree 401
Interactions of IP6 with Other Proteins and Macromolecules 402
Alterations in Levels of IP5 and IP6 402
Vesicle Trafficking: Exocytosis and Endocytosis 402
Cell Proliferation and Cell Cycle 405
Normalization of Cell Proliferation 405
DNA Synthesis 406
The Retinoblastoma Protein 406
Protein Kinase C 407
Ras Proteins 407
Induction of Cell Differentiation 408
Programmed Cell Death (Apoptosis) 409
PI 3-Kinase 409
Nuclear Inositol Signaling 410
mRNA Transport 410
Chromatin Remodeling 411
NF-kB (Nuclear Transcription Factor-kB) 411 Zinc-Finger Motif 412
DNA Repair 412
Role of IP6 in Energy Transduction 413
Anticancer Action of IP6: from the Laboratory to the Clinic 413
Other Biological Effects of IP6 415
Conclusion 415
References 415
INTRODUCTION
Inositol hexaphosphate (IP6, InsP6) is a polyphosphorylated carbohydrate, con-
tained in high concentrations (0.4-6.4%) in cereals and legumes. IP6 known
more commonly as “phytic acid” is the major form of phosphorous in the
seeds, wherein it is found as deposits of mixed “phytate” salts of K, Mg, Ca,
Mn, and Zn (1-3). In the plant kingdom, it is also found in other plant tissues
and organs such as pollen, roots, tubers, and turions (4). IP6 accumulates
during seed development and is broken down into lower inositol phosphates
during germination. The cytosol of almost all mammalian cells contain IP6 and
its lower phosphorylated forms (IP1 – 5) as well as the dephosphorylated form,
the parent compound-inositol. myo-Inositol is a cyclic alcohol (cyclitol) deriva-
tive of glucose. The enzyme myo-inositol(3)P1 synthase (MIPS) converts
glucose-6-phosphate to inositol(3)phosphate1 [Ins(3)P1]. In general, IP6 is con-
verted from inositol through the various polyphosphate intermediates via differ-
ent pathways in different organisms; these pathways are being more similar than
different. In addition to being a part of the phospholipids and eventually con-
verted to IP6 and its pyrophosphates, in the plant cells inositol is also utilized
in cell wall polysaccharides and other cyclitols. To the surprise of many in the
field of nutritional biochemistry, it has been a relatively recent finding that IP6 is not only present, but also is the most abundant of intracellular inositol phos-
phates in eukaryotes (5).
