Pepsinogen physiology

The results of the examinations of pepsinogen were formerly expressed by the + deviation from the normal value found in a healthy subject, which was accepted to be equal to zero, and the range of physiological values lay between - -35% and —35%. In the present procedure we united the expression of both pepsinogen and cathepsin in the form of an index, in which the normal value found in a healthy subject is ac-... 

See Hirschowitz BI. Secretion of pepsinogen, in Code CF (ed) Handbook of Physiology, Sec. 6, Alimentary Canal. Washington DC, American Physiological Society, 1967, Vol II, Secretion, pp 889-918, for a comprehensive review to about 1965. 

Under acidic conditions, pepsinogen is converted to pepsin by autocatalytic (i.e., intramolecular) catalysis, which results in loss of an additional NHz-terminal sequence. This conversion occurs slowly at pH values of 5 to 6 but very rapidly at pH 2. One of the NHz-terminal peptides released during the conversion possesses antipepsin activity. This peptide (MW 3,200) and its analogs complex with pepsin at pH values of 5.0 to 6.0 to inhibit catalytic activity. However, at lower pH, the inhibitor dissociates and is digested by pepsin. Thus, it seems unlikely that the inhibitor serves any significant physiologic function, at least in the adult stomach. 

An acid protease with an optimum pH of 2.5 was first described in human seminal plasma as pepsin and pepsinogen (1), but had not been purified or characterized. Recently, we have purified the acid protease and its proenzyme from human seminal plasma (2,3). In many respects, the properties of seminal plasma acid protease are similar to those of gastric pepsin. Since the proenzyme is more stable than the active enzyme in alkaline solution and can be converted into its active form in acidic solution, the acid protease is likely to exist in seminal plasma, at the physiological pH around 7.5 (4), in proenzyme form. 

Conversion of the proenzyme into its active form. We concluded that only the proenzyme form of acid protease can exist in human seminal plasma at the physiological pH of around 7.5 therefore, we investigated activation of proenzyme in acid medium. The purified proenzyme was incubated in 1 mM HCl, pH 3, for 1 hr, and then chromatographed on Sephadex G-50 column. The proenzyme was converted into an active form and some peptide of small molecular weight was released (Fig.2). As shown in Table II, when the amino acid analyses of the proenzyme, the active form, and activation peptide were carried out, the number of each amino acid residue of the proenzyme agreed well with the additive value between the number of that amino acid in the active form and activation peptide. This supported the conversion of the proenzyme to an active form. The amino acid composition of the active protease and of the proenzyme were comparable to those of bovine pepsin (10) and pepsinogen (11). However, definite differences are present. About forty residues which carried most of the basic amino acids, were released from pepsin, while sixty-nine residues, which carried about 30% of basic amino acid of the precursor were liberated from the proenzyme of seminal plasma acid protease. 

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