Phosphatidylinositols cleavage

Clycosyl-phosphatidylinositol Cleavage Products in Signal Transduction... 

Phosphatidylcholine (lecithin) is the most abundant phospholipid in membranes. Phosphatidylethanolamine (cephalin) has an ethanolamine residue instead of choline, and phosphatidylserine has a serine residue. In phosphatidylinositol, phosphatidate is esterified with the sugarlike cyclic polyalcohol myo-inositol. A doubly phosphorylated derivative of this phospholipid, phosphatidylinositol 4,5-bisphosphate, is a special component of membranes, which, by enzymatic cleavage, can give rise to two second messengers, diacylglycerol (DAG) and inositol l,4,5trisphosphate (InsPsi see p.386). 

Hydrolytic cleavage by phosphatidylinositol phospholipase C (PI-PLC) of the cyclic myo-inositol-l,2-phosphate (cIP) at C-2 is faster than that at C-1. A cyclic monofluorophosphonate has been prepared as a stable analogue of the substrate in... 

Stimulation of the oti-adrenoreceptors results in the activation of the Gq/n protein, which subsequently activates phospholipase CP (PLCP) and leads to cleavage of phosphatidylinositol-4,5-bisphosphate into inositol-1,4,5-trisphosphate (IP3) and... 

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. 

Activation of phospholipase C leads to cleavage of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG). 1P3 promotes release of Ca2+ from storage organelles, whereby contraction of smooth muscle cells, breakdown of glycogen, or exocytosis may be initiated. DAG stimulates protein kinase C, which phosphorylates certain serine- or threonine-containing enzymes. 

Agranoff, B.W., 1978, Textbook errors Cyclitol confusion. Trends Biochem. Sci. 3 N283-N285. Agranoff, B.W., Murthy, P.P.N., and Sequin, E.B., 1983, Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets. J. Biol. Chem. 258 2076-2078. 

Sharom, F.J., and Lehto, M.T., 2002, Glycosylphosphatidylinositol-anchored proteins Structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochem. Cell. Biol. 80 535-549. 

Phospholipase C catalyzes the cleavage of a phospholipid in the cell membrane, phosphatidylinositol-4,5-bisphosphate, generating diacylglycerol plus inositol-... 

R. A. Mortara, L. M. Minelli, F. Vandekerckhove, V. Nussenzwieg, and F. J. Ramalho-Pinto, Phosphatidylinositol-specific phospholipase C (PI-PLC) cleavage of GPI-anchored surface molecules of Trypanosoma cruzi triggers in vitro morphological reorganization of trypomastigotes, J. Eukaryot. Microbiol., 48 (2002) 27-37. 

Bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) (reviewed in ref. [51]) or trypanosomal GPI-specific phospholipase C (GPI-PLC) [52-54] releases GPI-anchored proteins from the cell surface leaving behind diacylglycerol. This cleavage not only solubilizes the protein, but also exposes a phosphoinositol-containing cryptic epitope termed cross-reacting determinant [55]. Reactivity of polyclonal antibodies derived against the cross-reacting determinant (CRD) provide additional evidence for the presence of a GPI anchor. 

Fig. 2. Enzymatic and chemical cleavage sites of GPI anchors useful in identifying GPI anchored membrane proteins. GPI-PLC, GPI-specific phospholipase C GPI-PLD, GPI-specific phospholipase D HF, hydrogen fluoride MONO, nitrous acid NaOH (NH3), mild alkali treatment PI-PLC, phosphatidylinositol-specific phospholipase C. (Redrawn from ref. [178].)...

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