RT Journal Article
SR Electronic
T1 Diethylaminoethoxyhexestrol inhibition of purified rat liver lysosomal phospholipase A1: role of drug binding to substrate.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 88
OP 92
VO 240
IS 1
A1 Kubo, M
A1 Hostetler, K Y
YR 1987
UL http://jpet.aspetjournals.org/content/240/1/88.abstract
AB 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.