Molecular phospholipase

Phospholipases. Table 1 Classification of low molecular mass phospholipase A2 isozymes that use catalytic His... 

Prescott, M. P. (ed.) A thematic series on phospholipases. Journal of Biological Chemistry 1997 Minireview Compendium. Bethesda, MD American Society for Biochemistry and Molecular Biology, 1997. 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

Excitable membranes maintain and rapidly modulate substantial transmembrane ion gradients in response to stimuli 576 Specific lipid messengers are cleaved from reservoir phospholipids by phospholipases upon activation by various stimuli 576 Phospholipids in synaptic membranes are an important target in seizures, head injury, neurodegenerative diseases and cerebral ischemia 576 Some molecular species of phospholipids in excitable membranes are reservoirs of bioactive lipids that act as messengers 576 Mammalian phospholipids generally contain polyunsaturated fatty acyl chains almost exclusively esterified to the second carbon of glycerol 577... 

Synaptic stimulation, ischemia or seizure activates phospholipase A2 and releases arachidonic and docosahexaenoic acids 578 Secretory phospholipases A2 are of relatively low molecular weight and have a high number of disulfide bridges, making them relatively more resistant to denaturation 579 There are high-affinity receptors that bind secretory phospholipase A2 579... 

Almost all receptor-mediated neutrophil functions are mediated via GTP-binding proteins (G-proteins), which provide the link between occupancy of plasma membrane receptors and the activation of intracellular enzymes, such as phospholipases and protein kinases. There are two groups of G-proteins those that are heterotrimeric and those with low molecular weight. 

Phosphoinositase C (i.e. phosphoinositide-specific phospholipase C [PLC]) enzymes are found in the vast majority of mammalian cells. Molecular cloning of these enzymes, analysis of their predicted amino acid sequences and immunological cross-reactivity indicate that at least three major forms of the enzyme exist PLC-/I, -8 and -y. Each of these enzyme types is encoded by a distinct gene. More recent experiments using the polymerase chain reaction and molecular cloning have revealed even greater enzyme di-... 

B. Waszkowycz, I. H. Hiller, N. Gensmantel, D. W. Payling, A Combined Quantum Mechanical/Molecular Mechanical Model of the Potential Energy Surface of Ester Hydrolysis by the Enzyme Phospholipase A2 ,. /. Chem. Soc., Perkin Trans. 2 1991, 225-231. 

Ortiz, A.R., Pastor, M., Palomer, A., Cruciani, G., Gago, F., and Wade, R.C. Reliability of comparative molecular field analysis models effects of data scaling and variable selection using a set of human synovial fluid phospholipase A2 inhibitors. /. Med. Chem. 1997, 40, 1136-1148. 

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