Inhibition of the Clostridium perfringens phospholipase C hydrolysis of a thiophosphate analog of lysophosphatidylcholine by micelle-bound ammonium and sulfonium cations.
Cetyltrimethylammonium and n-octadecyldimethylsulfonium bromides inhibit the Clostridium perfringens phospholipase C-catalyzed hydrolysis of 1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol (1) at pH 7.5, 37 degrees C, mu = 0.15 with KCl. Mixed micelles containing 1 and either inhibitor are substrates for the enzyme and the fraction of activity remaining is a monotonic, but non-linear function of the mole fraction of inhibitor. Simple saturation kinetics are observed as the concentration of 1 is increased in mixed micelles containing a constant mole fraction of inhibitor. Inhibition constants for cetyltrimethylammonium and n-octadecyldimethylsulfonium bromides are 0.66 +/- 0.04 and 0.25 +/- 0.02 mM, respectively. The data suggest that the significant inhibition previously observed for soluble alkyldisulfonium salts (K50 for dodecamethylene-bis(dimethylsulfonium) bromide, 27 microM) is dependent upon bifunctional cationic interactions rather than hydrophobic binding.
Young
P R
PR
Department of Chemistry, University of Illinois, Chicago 60680.
Snyder
W R
WR
McMahon
R F
RF
D002412:Cations / Q000494:pharmacology; D003016:Clostridium perfringens / Q000201:enzymology*; D005227:Fatty Acids / Q000378:metabolism*; D007700:Kinetics; D008823:Micelles; D010767:Phosphorylcholine / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D013452:Sulfonium Compounds / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D002412:Cations; D005227:Fatty Acids; D008823:Micelles; D000644:Quaternary Ammonium Compounds; D013452:Sulfonium Compounds; D010767:Phosphorylcholine; C073834:1-S-phosphocholine-2-O-hexadecanoyl-1-mercapto-2-ethanol; D010738:Type C Phospholipases