Phosphatidylinositol, cleavage products

Clycosyl-phosphatidylinositol Cleavage Products in Signal Transduction... 

Intracellular Messengers from Phosphatidylinositols When the hormone vasopressin stimulates cleavage of phosphatidylinositol 4,5-bisphosphate by hormone-sensitive phospholipase C, two products are formed. What are they Compare their properties and their solubilities in water, and predict whether either would diffuse readily through the cytosol. 

Answer Phosphatidylinositol 4,5-bisphosphate is a membrane lipid. The two products of cleavage are a diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diacylglycerol is not water-soluble and remains in the membrane, acting as a second messenger. The IP3 is highly polar and very soluble in water it readily diffuses in the cytosol, acting as a soluble second... 

While these results support a phosphate ester bridge between the glycerol and inositol, it does not prove where the bond is located on the inositol molecule. Inasmuch as the inositol phosphate isolated by alkaline cleavage from the parent phosphatidylinositol or the glycerophosphoinositol was optically active, the phosphate must be attached at the 1 or 4 position. Substitution at the 2 position of inositol would not yield an optically active product. Subsequently as will be discussed, observations from several laboratories have shown that the phosphate bond is between the sn- 3 position of the glycerol and the C-l hydroxyl on myo-inositol. 

When acetylcholine-stimulated breakdown of phosphatidylinositol was first observed in the avian salt gland, it seemed logical to assume that this would be by cleavage of phosphatidylinositol to form diglyceride and inositol phosphate (Hokin, M.R. Hokin, L.E., 1964). A Ca -dependent enzyme with phospholipase C type activity which catalyzed this reaction had been demonstrated by Kemp et al. (1961). More recently, Dawson et al. (1971) showed that the products are inositol 1,2-cyclic phosphate, inositol 1-phosphate and diglyceride. There is an enzyme with these properties in mouse pancreas. The enzyme is not activated by acetylcholine in soluble extracts, and we have found no evidence that it is concerned in acetylcholine-stimulated breakdown of phosphatidylinositol in the intact cell, nor that the function of phosphatidylinositol breakdown is to form inositol 1,2-cyclic phosphate, as has been suggested by Michell Lapetina (1972). 

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