Competitive inhibition of lipolytic enzymes. V. A monolayer study using enantiomeric acylamino analogues of phospholipids as potent competitive inhibitors of porcine pancreatic phospholipase A2.
For the first time, we have shown that a stereospecific interaction occurs between porcine pancreatic phospholipase A2 and a monomolecular film of amidophospholipid used as inhibitor. Direct binding experiments, using radiolabelled phospholipase A2, showed that 13 times more enzyme was bound to phospholipid films of the L series by comparison with films of the D series. These results were confirmed by indirect binding studies using re-spreading experiments. Kinetic studies of the porcine pancreatic PLA2, using enantiomeric acyl-amino phospholipid analogues, have shown that: (1) inhibitors of the L series are more potent than inhibitors of the D series, (2) inhibitors having a negative charge are more potent than zwitterionic inhibitors, (3) inhibitory power values are greater when evaluated in micellar system than in a the monolayer system, (4) the inhibitory power increases continuously with surface pressure.
Ransac
S
S
Centre de Biochimie et de Biologie Moléculaire, C.N.R.S., Marseille, France.
Deveer
A M
AM
Rivière
C
C
Slotboom
A J
AJ
Gancet
C
C
Verger
R
R
De Haas
G H
GH
D000818:Animals; D007700:Kinetics; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000494:pharmacology*; D013379:Substrate Specificity; D013552:Swine
D010743:Phospholipids; D010741:Phospholipases A; D054467:Phospholipases A2