In mammals, the main eicosanoid pre

In mammals, the main eicosanoid precursor is arachidonic acid (5,8,11,14-eicosatetraenoic acid), a 20-carbon unsaturated fatty acid containing four double bonds (hence eicosa,  referring to the 20 carbon atoms, and tetraenoic, referring  to the four double bonds). In most cell types, arachidonic  acid is esterified in the phospholipid pool, and the concentration of the free acid is low. The principal eicosanoids are  the  prostaglandins,  the  thromboxanes  and  the  leukotrienes,  although other derivatives of arachidonate, for example  the  lipoxins,  are  also  produced.  (The  term  prostanoid  will be used here to encompass both prostaglandins and  thromboxanes.) In most instances, the initial and rate-limiting step in  eicosanoid  synthesis  is  the  liberation  of  arachidonate,  usually in a one-step process catalysed by the enzyme phospholipase A2 (PLA2; Fig. 17.2), although a multi-step process  involving phospholipases C or D in conjunction with diacylglycerol  lipase  is  sometimes  utilised.  Several  species    of  PLA2  exist,  but  the  most  important  is  probably  the  highly regulated cytosolic PLA2. This enzyme generates not  only  arachidonic  acid  (and  thus  eicosanoids)  but  also  lysoglyceryl-phosphorylcholine  (lyso-PAF),  the  precursor  of  platelet activating factor,  another  inflammatory  mediator  (see Fig. 17.2). Cytosolic PLA2 is activated (and hence arachidonic acid  liberated) by phosphorylation. This occurs in response to  signal transduction events triggered by many stimuli, such  as thrombin action on platelets, C5a on neutrophils, bradykinin  on  fibroblasts  and  antigen–antibody  reactions  on  mast cells. General cell damage also triggers the activation  process.  The  free  arachidonic  acid  is  metabolised