title: Diethylaminoethoxyhexestrol inhibition of purified rat liver lysosomal phospholipase A1: role of drug binding to substrate.
abstract: 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.
mesh_terms: 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
chemical_list: D006589:Hexestrol; D010740:Phospholipases; D010741:Phospholipases A; D054466:Phospholipases A1; C100116:hexestrol bis(diethylaminoethyl ether)