The bile acid phospholipid conjugate ursodeoxycholate lysophoshatidylethanolamide acts by binding to calcium independent membrane phospholipase A2 type beta

Background: The hallmarks of non-alcoholic steatohepatitis are inflammation, ongoing liver cell damage, and the accumulation of hepatic fat. Although the pathogenesis is not fully understood yet, there is clear evidence that disease progression is associated with an increased ratio of lysophosphatidylcholine (LPC) to phosphatidylcholine (PC), which is an indicator of elevated phospholipase A2 (PLA2) activity. The isoform iPLA2β is a member of the fatty acid uptake complex and has an intrinsic capability to generate LPC, while the bile acid phospholipid conjugate, ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) inhibits iPLA2β and suppresses pro-inflammatory LPC generation in a dose-dependent mode. However, the precise mode of activity of this inhibition is still enigmatic. Methods: In the present study, we used in silico techniques for predicting the potential docking sites of UDCA-LPE in iPLA2β. Results: We identified a region between Phe84 and Leu125 that should have a large affinity for UDCA-LPE. The proposed docking site is nearly identical with those that were determined for binding of pyrrophenone to the evolutionarily conserved PLA2α. Conclusions: The affinity of UDCA-LPE for iPLA2β might explain the rationale for the efficacy of UDCA-LPE in preventing hepatic fatty acid uptake.