Pepsin Inhibitors from Ascaris lumbricoides

Each of the four Ascaris pepsin inhibitors forms a stoichiometric complex with porcine pepsin between pH 2 and 5 with an apparent dissociation constant, Ki, of 10-10 m, when free pepsin was determined with hemoglobin, or 9.1 x 10-10 m when free pepsin was determined with N-acetyl-l-phenylalanyl-l-diiodotyrosine. Each inhibitor forms a stoichiometric complex with human pepsin and with porcine gastricsin with dissociation constants for the complexes of the order of 10-9 m but does not react with human gastricsin. All of the inhibitors delayed milk-clotting activity of porcine pepsin at pH 5.3. The pepsin-inhibitor complex forms between pH 2 and 5 in less than 20 s and is completely dissociated in 30 min at pH 8.8 and 37°. The fully active inhibitor is recovered at low pH, but pepsin is denatured. No evidence could be obtained to suggest that the inhibition of pepsin by these Ascaris inhibitors is a recognizable case of temporary inhibition.