Diethylaminoethoxyhexestrol inhibition of purified rat liver lysosomal phospholipase A1: role of drug binding to substrate.
In this report, the inhibition of purified rat liver phospholipase A1 by diethylaminoethoxyhexestrol (DH) has been evaluated and the results correlated with DH binding to sonicated vesicles of di[1-14C]oleoylphosphatidylcholine. The drug bound in a positive cooperative manner to two classes of binding sites on phosphatidylcholine small unilamellar vesicles, one having an apparent high affinity and low capacity and another having a low affinity and high capacity. The observed data were shown to fit to a mixed type of inhibition when the free DH concentration (determined independently in the binding experiments) was used instead of the total drug concentration. Hydrolysis of enzyme-substrate-drug complexes was estimated to occur at a rate only half that of the enzyme-substrate complex. Results with DH suggest that both drug-enzyme and drug-substrate interactions may be important factors in the inhibition of lysosomal phospholipase A1.
D000818:Animals; D006589:Hexestrol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology*; D008433:Mathematics; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054466:Phospholipases A1; D011485:Protein Binding; D051381:Rats
D006589:Hexestrol; D010740:Phospholipases; D010741:Phospholipases A; D054466:Phospholipases A1; C100116:hexestrol bis(diethylaminoethyl ether)