Inhibition of Pepsinogen Activation by Gossypol

Abstract

Incubation of pepsinogen with gossypol, a polyphenolic compound of plant origin, resulted in an inhibition of the autocatalytic conversion of pepsinogen to pepsin that takes place at low pH values. Essentially complete inhibition of the activation process occurred in reaction mixtures containing 2:1 to 3:1 molar ratios of gossypol to pepsinogen in the presence of 10% ethanol; the interaction between gossypol and the zymogen occurred most readily at pH 8.0 and 35°. Extensive dialysis of gossypol-pepsinogen preparations failed to remove the gossypol, and the gossypol-pepsinogen preparations were hydrolyzed much less extensively by trypsin and papain than was pepsinogen under identical conditions. Determinations of free e-NH2 groups in the gossypol-pepsinogen preparations suggested that lysyl residues are involved in the binding of gossypol to pepsinogen. From the evidence presented, it appears that gossypol reacts with pepsinogen only after the protein has undergone a change in conformation and that after reaction has occurred, the conformation of native pepsinogen cannot be reestablished.