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Enzyme Overlap Generates New Signals

May 13, 2011 | Leigh McMillan

Two newly discovered lipid signaling molecules may have roles at sites of inflammation, Claus Schneider, Ph.D., and colleagues report in the April 26 Proceedings of the National Academy of Sciences.

The enzymes COX-2 and 5-LOX initiate the production of prostaglandins and leukotrienes, respectively – lipid compounds that have inflammatory and immune system-regulatory effects in both normal physiology and disease (e.g. atherosclerosis, cancer). The COX-2 and 5-LOX pathways were previously considered distinct, but the current research shows they overlap: COX-2 can act on a product of 5-LOX to produce two new “hemiketal” compounds called HKD2 and HKE2 (they are structurally similar to the prostaglandins PGD2 and PGE2).

HKD2 and HKE2 were produced in activated human white blood cells, and their synthesis was blocked by inhibitors of COX-2 or 5-LOX. HKD2 and HKE2 stimulated migration of vascular endothelial cells and formation of tubular structures, suggesting that these new lipid signals may promote blood vessel formation at sites of inflammation.