Of phosphatidylinositols

These groups were designed for use in the synthesis of phosphatidylinositol phosphates, where it was desirable to be able to cleave a benzoate without cleaving a glyceryl ester. 

Phosphatidylinositol 4,5-bisphosphate is a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at positions 4 and 5. 

P2 is generated from PtdIns(4)P by the enzymatic activity of phosphatidylinositol 4-phosphate 5-kinase (PDP5K) (Fig. 1). Additional pathways are likely to be discovered. 

Hormonal factors and other stimuli by activating phospholipase C-(3 or -y isoforms stimulate the breakdown of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol, a reaction called PI response. 

TRPVl, also known as the capsaicin- or vanilloid-receptor, is a nonselective cation channel expressed e.g., in neurons of the dorsal root and trigeminal ganglions, which integrates multiple pain-producing stimuli including heat, protons, capsaicin, and resiniferatoxin. In addition, TRPVl currents can be activated by ananda-mide, protein kinase C (PKC), and by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). 

Covalent regulation. Following occupation and activation of the M2 acetyl choline receptors, phospholipase C (PLC), is activated and both inositol (l,4,5)-trisphosphate (IP3), and diacylglycerol (DAG), are formed by hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2). 

Activation of Neutrophils Is Similar to Activation of Platelets Involves Hydrolysis of Phosphatidylinositol Bisphosphate... 

Number of papers to date have shown that the CXCR4 receptors expressed in both neuronal and glial cells are functional and coupled to multiple intracellular pathways (Lazarini et al. 2003). The CXCR4 through pertussis toxin (PTX)- sensitive G proteins is coupled to at least two distinct signaling pathways (1) the first pathway, involving the activation of phosphatidylinositol- 3 (PI-3) kinase and extracellular signal... 

Inositol triphosphate (IP3)-gated channels are also associated with membrane-bound receptors for hormones and neurotransmitters. In this case, binding of a given substance to its receptor causes activation of another membrane-bound protein, phospholipase C. This enzyme promotes hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3. The IP3 then diffuses to the sarcoplasmic reticulum and opens its calcium channels to release Ca++ ions from this intracellular storage site. 

Arcaro, A., and Wymann, M. P. (1993). Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor The role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses. Biochem. J. 296, 297—301. 

Zaikova, T. (2001). Synthesis of fluorogenic substrates for continuous assay of phosphatidylinositol-specific phospholipase C. Bioconjug. Chem. 12, 307-313. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

The relatively small pool of the precursor for Ins(l,4,5)P3, the phospholipid PtdIns(4,5)P2, is synthesized from the larger reservoir of phosphatidylinositol (Ptdlns) and, therefore, the supply of PtdIns(4,5)P2... 

When the receptor interacts with its associated G protein, the conformation of the guanine-nucleotide-binding site is altered. The subunits then dissociate, and a phosphatidylinositol-specific phospholipase C (PI-PLC) is activated [5]. The subsequent hydrolysis of phosphatidylinositol bisphosphate then produces inositol triphosphate (IP3) and diacylglycerol (DAG), which are known to be secondary messengers. For example, the water soluble IP3 is released into the cell where its ultimate targets are the calcium storage organelles from which Ca2+ is released [3]. The presence of DAG in cells is known to activate the cellular enzyme protein kinase C (PKC) [6, 7], which phosphorylates a number of cellular... 

The rate of production of DAG in the cell does not occur linearly with time, but rather it is biphasic. The first peak is rapid and transient and coincides with the formation of IP3 and the release of Ca2+ this DAG is therefore derived from the PI-PLC catalyzed hydrolysis of phosphatidylinositols [1]. There is then an extended period of enhanced DAG production that is now known to be derived from the more abundant phospholipid phosphatidylcholine (PC), which has a different composition of fatty acid side chains [9]. Although DAG may be generated directly from PC through the action of PC-PLC, it can also be formed indirectly from PC. In this pathway, PC is first hydrolyzed by PLD to give choline and phosphatidic acid, which is then converted to DAG by the action of a phos-phatidic acid phosphatase [10,11 ]. 

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