Rabbit pepsinogens. Purification, characterization, analysis of the conversion process to pepsin and determination of the NH2-terminal amino-acid sequences.

Six pepsinogens were purified from the gastric mucosa of adult rabbits by chromatographies on DEAE-cellulose, DEAE-Sephacel and Sephadex G-150. They were designed as pepsinogen I, pepsinogens II-1, II-2, II-3, and II-4, and pepsinogen III, based on their chromatographic behaviors. Each pepsinogen was converted to pepsin at pH 2.0 and 14 degrees C. The resulting pepsins had roughly similar enzymatic properties. However, activation processes appeared to differ significantly among them. Pepsinogen I was converted to an active intermediate form by sequentially releasing the NH2-terminal 25 or 26 residues. This active form was fairly stable and no further conversion occurred on further incubation for several hours. Pepsinogens II were converted to pepsins partly sequentially through intermediate forms and partly directly releasing the NH2-terminal 44 residues as a single intact polypeptide. Pepsinogen III appeared to be converted to pepsin directly without forming intermediate species. The amino acid sequences of the activation segments of these pepsinogens were determined together with the sequences in the NH2-terminal regions of the resulting pepsins. Five distinct sequences were identified, indicating that most of these pepsinogens are the products of different genes.