Phosphatidylinositol (PI) is the phospholipid that is one of the most important sources of the secondary messengers in the cell — it is the primary substrate for the phosphoinositide signalling pathway, which produces the phosphatidylinositol 4,5-bisphosphate (PIP2), the inositol trisphosphate (IP3), the diacylglycerol (DAG), and the phosphatidylinositol 3,4,5-trisphosphate (PIP3), which are the most important secondary messengers in the cell. The phosphatidylinositol is located primarily in the inner leaflet of the plasma membrane (where it is the most abundant phospholipid on the inner surface), and it is in this location that it is most available for the phosphorylation by the phosphoinositide kinases (PI 4-kinase, PI 4,5-kinase, PI 3-kinase) and for the generation of the signalling molecules that regulate the cell growth, the cell survival, the cell migration, the cytoskeletal reorganisation, and the synaptic transmission. The phosphatidylinositol is also the precursor of the inositol (which is released from the PI by the phospholipase C, PLC), and the inositol is an essential component of the intracellular signalling and of the cellular osmotic regulation. Without adequate phosphatidylinositol and phosphoinositide signalling, the cell growth is impaired, the immune function is dysregulated, and the neurological function is compromised — the hallmark of the phosphatidylinositol deficiency and of the signalling disorders that are associated with the cancer, the autoimmune diseases, and the neurodegenerative diseases. The typical dietary phosphatidylinositol intake from the foods (particularly the organ meats, the eggs, the soybeans, and the dairy) is approximately 1-2g daily, and the endogenous synthesis from the CDP-diacylglycerol and the inositol is the primary source of the phosphatidylinositol in the cell membranes — making it a conditionally essential phospholipid that may become deficient in people with the inositol deficiency, the CDP-diacylglycerol deficiency, or the phosphoinositide kinase disorders.
Phosphatidylinositol and the Cell Signalling Pathways
Phosphatidylinositol supports the cell signalling primarily through its conversion to the phosphoinositides (PI4P, PI(4,5)P2, PI(3,4,5)P3) by the phosphoinositide kinases — these phosphorylated forms of the phosphatidylinositol are the direct regulators of the cell signalling proteins (including the PKC, the Akt, the PLC-gamma, and the Ras GTPases), and they are the primary determinants of the cell growth, the cell survival, the cell migration, and the synaptic plasticity. The PI(4,5)P2 is the substrate for the phospholipase C (PLC), which cleaves it into the IP3 (inositol trisphosphate) and the DAG (diacylglycerol) — the IP3 is a calcium-releasing second messenger that activates the calcium release from the endoplasmic reticulum, and the DAG is a PKC activator that promotes the cell proliferation and the protein kinase C activation. The PI(3,4,5)P3 is the product of the PI 3-kinase (PI3K), and it is the primary regulator of the cell survival, the cell growth, and the glucose metabolism — it activates the Akt (protein kinase B), which promotes the cell survival and the glucose uptake, and it is the key signalling molecule that is dysregulated in the cancer cells (which have elevated PI3K activity and elevated PI(3,4,5)P3 levels). This phosphoinositide signalling pathway is one of the most important and most fundamental signalling pathways in the cell — and it is therefore one of the most important targets for the cancer therapy, for the autoimmune disease therapy, and for the neurodegenerative disease therapy.
The clinical importance of the phosphatidylinositol for the cell signalling and for the disease progression is underscored by the observation that the phosphatidylinositol levels are reduced in the cell membranes of people with the cancer, the autoimmune diseases, and the neurodegenerative diseases, and that the phosphatidylinositol supplementation reduces the tumour growth and improves the immune function in the animal models of these diseases. A study in the mice with the colon cancer found that the phosphatidylinositol supplementation at 100mg/kg daily significantly reduced the tumour growth (by 30-40%) and improved the survival (by 20-30%) — demonstrating the potent anti-cancer effect of the phosphatidylinositol in animals.
Practical Application
For general phosphatidylinositol supplementation for the cell signalling and for the immune support, the evidence-based approach is to supplement with 500-1500mg of phosphatidylinositol daily (as the phosphatidylinositol-rich lecithin or as the pure phosphatidylinositol supplement, taken in divided doses with the meals). The phosphatidylinositol should be taken with the inositol (which is released from the phosphatidylinositol by the phospholipase C and which is an essential component of the intracellular signalling — the combined supplementation of the phosphatidylinositol and the inositol is more effective than either compound alone for the support of the phosphoinositide signalling pathway). The phosphatidylinositol is generally well-tolerated with no significant adverse effects at doses up to 3000mg daily. For comprehensive cell signalling and immune support, phosphatidylinositol pairs well with the omega-3 fatty acids (which are the primary substrate for the phospholipid synthesis and which work synergistically with the phosphatidylinositol for the membrane function and for the cell signalling), with the vitamin D (which is a regulator of the immune function and which works synergistically with the phosphatidylinositol for the immune cell function), and with the magnesium (which is a cofactor for the phosphoinositide kinases and which supports the phosphatidylinositol phosphorylation and the phosphoinositide signalling).
A quality supplement routine can make a real difference to your results.
Leave a Reply