1. Celecoxib shunts arachidonic acid from the COX-2 pathway to the 5-LOX pathway.
Celecoxib shunts arachidonic acid from the COX-2 pathway to the 5-LOX pathway. Arachidonate, which is released from cell membrane stores (top; the membrane shows protein structures unrelated to this shunt) by the action of phospholipase A2 (PLA2), is oxygenated by COX-2 or 5-LOX. Some of the products of the COX-2 pathway (most notably, PGI2) exert cardiovascular protective activities, whereas the products of the 5-LOX pathway are associated with enhanced cardiovascular risk. Blocking COX-2 action with an inhibitor such as celecoxib increases the flux of arachidonic acid through the 5-LOX pathway. The oxygenation of arachidonate via the two pathways can be monitored by the levels of the urinary biomarkers PGE-M and LTE4. The figure does not mean to imply that COX-2 and 5-LOX are located in the same cells.
Lawrence J. Marnett Cancer Prev Res 2009;2:
©2009 by American Association for Cancer Research