Esterases in Schistosomes: Reaction with Substrates and Inhibitors

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Abstract
Studies were made (at 37 degrees, pH 7.6) on the interaction of some organophosphorus compounds and carboxylic acid esters with cholinesterases (EC 3.1.1.7 and EC 3.1.1.8) and A-esterases (EC 3.1.1.2) in homogenates of Schistosoma mansoni (adults and cercariae) and Schistosoma haematobium (adults). The results are compared with those obtained from the same reactions in other parasitic helminths and in mammalian tissues. Metrifonate (0,0-dimethyl-2,2,2-trichloro-1-hydroxyethyl phosphonate) does not seem to react with cholinesterases from parasites or mammals. Dichlorvos (0,0-dimethyl-2,2-dichlorovinyl phosphate) is a phosphorylating inhibitor; the rate constants of inhibition of cholinesterases from schistosomes are in the order of 10(5) M-1 min.-1. Similar or lower rate constants (10(4) M-1 min.-1) are found for cholinesterase inhibition in other parasitic helminths and mammals. S. mansoni and S. haematobium hydrolyse carboxylic acid esters (10 mM) in decreasing order: phenylacetate (about 2 mumol per hour per mg protein), acetylthiocholine, propionylthiocholine, butyrylthiocholine. Dichlorvos (10 mM) is hydrolysed by S. mansoni and S. haematobium at about the same rate as by mammalian erythrocytes and human sera (about 10 mumol per hour per gram wet weight). Neither paraoxon (0,0-diethyl-4-nitrophenyl phosphate) nor methyl-paraoxon are hydrolysed by S. mansoni and S. haematobium, although both compounds are good substrates for mammalian A-esterases. The stability of metrifonate and dichlorvos in buffer solutions was also determined (at 37 degrees). Metrifonate is about equally stable in bicarbonate buffer (pH 7.6) and phosphate buffer (pH 7.4) (t 1/2 = 1.5 and 2.6 hrs, respectively), while dichlorvos is considerably more stable in bicarbonate (t 1/2 = (36 hrs) than in phosphate buffer (t 1/2 = 2.9 hrs).