Phosphoinositides Degradation

During hormonal stimulation of Ptdlns 4,5-P2 hydrolysis there appears to be a preferential degradation of molecules, such as diacylglycerol and phosphatidic acid, which contain arachidonate in the 2-position. Two separate pathways have been proposed for the release of arachidonic acid from these two products of the phosphoinositide response. The first proposes that diacylglycerol is the source of the liberated arachidonate and that diacylglycerol lipase acts on the DG released by hydrolysis of phosphoinositides. The second suggests that a phosphatidic acid-specific phospholipase A2 is responsible for cleaving the arachidonic acid from phosphati-date. 

The signal-transduction processes in the liver are more complex than those in muscle. Epinephrine can also elicit glycogen degradation in the liver. However, in addition to binding to the p-adrenergic receptor, it binds to the 7TM a-adrenergic receptor, which then initiates the phosphoinositide... 

In 1953, Hokin and Hokin reported that the application of acetylcholine to pigeon pancreatic tissue slices resulted in a rapid incorporation of radioactive [32p]orthophosphate into membrane phosphoinositides and phosphatidic acid (Hokin and Hokin, 1953). From these observations they hypothesized that the effect of acetylcholine was due to the rapid degradation and resynthesis... 

Evidence is accumulating that pools of phosphoinositides can be rapidly synthesized and degraded in discrete membrane domains or even subnuclear areas through different metabolic pathways (Figure 3). For instance, upon agonist-mediated cell stimulation, PI 3-kinase can rapidly and transiently... 

Figure 7. Degradation of phosphoinositides. Figures in parentheses refer to equations in Text.

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