Phospholipase , general

Figure 43-7. Phospholipase C cleaves PIPj into diacylglycerol and inositol trisphosphate. R, generally is stearate, and Rj is usually arachido-nate. IP3 can be dephosphorylated (to the inactive I-1,4-P2) or phosphorylated (to the potentially active I-1,3,4,5-P4).

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... 

Although there are several classes of phospholipases, the phospholipase C (PLC) family is the one that has recently received intense scrutiny in the general context of signal transduction. The present account therefore details recent structural and mechanistic studies of one member of this important super family of enzymes, the phosphatidylcholine-preferring phospholipase C from B. cereus (PLCB(.). 

Methods used to demonstrate the existence of membrane phospholipid asymmetry, such as chemical labelling and susceptibility to hydrolysis or modification by phospholipases and other enzymes, are rmsuitable for dynamic studies because the rates of chemical and biochemical reactions are of a different order compared to the transmembrane translocahon of the phospholipids. Indirect methods have therefore been developed to measure the translocation rate which are consequent on the loss of membrane phospholipid asymmetry. Thus time scales appropriate to rates of lipid scrambling under resting conditions or when the forces preserving the asymmetric phospholipid distribution are disturbed can be monitored. Generally the methods rely on detecting the appearance of phosphatidylserine on the surface of cells. Methods of demonstrating Upid translocation in mammalian cells has been the subject of a recent review (Bevers etal., 1999). 

Stingrays Dasyatidae Not a phospholipase Protein Defense in general Pain, death (1%)... 

The nature of the second messenger response to a given neurotransmitter depends on the subtype of receptor to which it binds and the G protein to which the receptor is coupled. Three of the most commonly utilized G proteins include G, which stimulates adenylyl cyclase to produce cyclic AMP (cAMP) Gj, which inhibits adenylyl cyclase, resulting in lower intracellullar levels of cAMP and Gq, which activates phospholipase C to produce the second messengers IP3 and DAG. In general, these activities refer to the function of the a subunit however, it should be pointed out that the py complex has its own set of activities (on adenylyl cyclase, phospholipase C, channels, mitogen-activated protein kinase [MAPK]) that are just now becoming better clarified. 

The members of the G, subfamily are not modifiable by pertussis toxin or cholera toxin. The signal protein next in the reaction sequence is generally the P-type of phospholipase C. 

A model that is consistent with these observations of the action of trypsin and phospholipase A and with the discontinuities in the All-composition curves (Figures 2 and 3) is one in which the lipid monolayer is not a continuous palisade of uniformly oriented lipid molecules but rather an assembly of surface micelles. In this model, proposed by Colacicco (4, 5), the protein first comes into contact with the lipid molecules at the periphery of the surface micelles and then inserts itself as a unit between them. This is the basis for the generalized nonspecific interaction between lipids and proteins which results in increase of surface pressure. One may thus explain the identical All values obtained with films of lecithin and 80 mole % lactoside by picturing the lecithin molecules outside and the lactoside molecules inside the surface micelles. In this model lecithin prevents the bound lactoside from interacting nonspecifically with globulin and produces the same increase in pressure as with a film of pure lecithin. In the mixed micelle the lactose moiety of the lactoside protrudes into the aqueous subphase. Contact of the protein with these or other nonperipheral regions of the surface micelle would not increase the surface pressure. 

The dietary precursor of the eicosanoids is the essential fatty acid, linoleic acid. It is elongated and desaturated to arachidonic acid, the immediate precursor of prostaglandins, which is stored in the membrane as a component of a phospholipid—generally phosphatidyl-inositol (PI). Arachidonic acid is released from PI by phospholipase A2. 

Two pathways from the activated receptor are shown. At the left is activation of phospholipase Cy and formation, at a membrane-bound site, of inositol trisphosphate and diacylglycerol (DAG). The main pathway, in the center, activates Ras with the aid of the G protein Sos. Activated Ras, in turn, activates Raf and successive components of the MAPK cascade. At the right a seven-helix receptor activates both phospholipase C(3 and Ras via interaction with a (3y subunit. (B) A generalized scheme for the MAP kinase pathway. See Seger and Krebs.380... 

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