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Arachidonic
Acid Metabolism:
Arachidonic acid metabolism is an important source of
inflammatory mediators.
Arachidonic acid is derived from dietary sources and
is incorporated into the plasma membrane of many cells in the body, including
inflammatory cells, by esterification to phosphatidylcholine. For arachidonic
acid metabolism to occur, it must be released from its esterified position
in the cell membrane. Cleavage of arachidonic acid from the cell membrane
is accomplished principally by phospholipase A2. Phospholipase A2 is switched
on to release arachidonic acid by mechanical, chemical or physical stimuli
or by inflammatory mediators such as the complement component C5a.
Once freed from the cell membrane, arachidonic acid
can undergo metabolism down one of two major pathways:
-
cyclo-oxygenase - synthesizing prostaglandins
and thromboxanes
-
lipoxygenase - synthesizing leukotrienes and
lipoxins
The arachidonic acid metabolism pathway is the target of many of the
pharmacological agents that seek to modulate inflammation:
-
One of the actions of corticosteroids is to inhibit the action of
phospholipases, preventing the release of arachidonic acid from the
plasma membrane.
-
Many of the non-steroidal anti-inflammatory drugs
(NSAIDs), target the cyclo-oxygenase pathway, inhibiting the production
of prostaglandins and thromboxanes (e.g. aspirin, Rimadyl, Metacam).
 
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