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.
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Diethylaminoethoxyhexestrol inhibition of purified rat liver lysosomal phospholipase A1: role of drug binding to substrate.
