Proteins that Modulate Phospholipase A2 Activity

Activation of the various PLA2 isoforms described in the preceding sections provides a single-step pathway of arachidonate mobilization. In addition to this direct mechanism, arachidonate mobilization may be initiated by the stimulation of PLCs, which 

In those experiments, neurons obtained from the spinal cord of embryonic rats were labeled by incubation with various radioactive lipid precursors, and exposed to bradykinin. Application of this peptide raised the levels of unesterified arachidonate, but had no effect on lysophospholipids, arguing against an involvement of PLA2. By contrast, appearance of the free fatty acid was preceded by a transient increase in 1,2 diacylglycerol content which took place within a few seconds of exposure to bradykinin. Because of its rapid time-course, this rise in 1,2 diacylglycerol may derive from the direct stimulation of a PLC activity. 

It should be added, however, that the appearance of 1,2 diacylglycerol is, in general, insufficient to conclusively infer an involvement of the PLC/acylglycerol pathway the most resilient difficulty 

Hydrolysis of phospholipids by PLDs—a family of enzymes of which none has yet been purified to homogeneity (but this is probably going to change in the near future)—produces phosphatidic acid and a non-phosphorylated polar head compound, such as choline or ethanolamine (Fig. 2.4 and 2.8). Needless to say, phosphatidic acid is biologically active (among other things, it stimulates protein phosphorylation), but we shall focus here only on its role as arachidonic acid precursor. Two enzymatic pathways are involved (Fig. 2.8). 

A phosphohydrolase activity cleaves the phosphate ester bond of phosphatidic acid forming 1,2 diacylglycerol, which may then enter its usual metabolic route the reaction goes both ways, and phosphatidic acid may be synthesized from 1,2 diacylglycerol by the action of a lipid kinase (Fig. 2.8). As mentioned, this two-way shunt plays havoc with the attempts to determine unequivocally whether 1,2 diacylglycerol and phosphatidic acid derive from the activation of PLC or PLD.  

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