Human gastricsin

The amino acid compositions vary widely and do not indicate any relationship among the enzymes. However, there is one unusual feature. In four proteins the basic amino acid content is exceptionally low. Human gastricsin and human pepsin have no lysine and contain only one histidine and three arginine residues per molecule. Porcine pepsin has one lysine, one histidine, and two arginine residues. Penicillopepsin has five lysines, three histidines, and no arginine. The significance of this unusual feature, which is not shared by other acid proteases, is not clear. 

Fig. 4. Heat inactivation of human pepsin (I) and gastricsin (II) at pH 2.0 and 3.2. The enzyme solutions were incubated for 10 minutes at the indicated temperature and the proteolytic activity measiued. The losses of activity were expressed as percent of the inactivation relative to that of the solution incubated at 45°. From Tang et al. (T6).

T5, Tang, J., Wolf, S., Caputto, H., and Trucco, R. E., Crystallization of gastricsin from human gastric juice. Federation Proc. 18, 337 (1959). Abstr. 

Fig. 24. Immunoelectrophoresis of human gastric juice. Immunoelectrophoietic patterns A, in vitro depepsinized normal gastric juice B, crystalline human pepsin C, crystalline human gastricsin D, human serum albumin E, glandular mucoprotein F, mucoproteose C, rapid vitamin Bj2 binder H, slow vitamin B 2 binder. Anti-gastric juice immune serum was used throughout. From Simons and Grasbedc (S9).

Tang J, Wolf S, Caputto R, et al. Isolation and crystallization of gastricsin from human gastric juice. J Biol Chem 234 1174-1178, 1959. 

Huang W, Tang J. On the specificity of human gastricsin and pepsin. J Biol Chem 244 1085-1091, 1968. 

Partial structures of human gastricsin and bovine pepsinogen B have been determined. 

Human pepsin C = Human gastricsin (Hum. pep. Residues 46-70 (53), residues 355-373 (54). Personal communications, P. Sepulveda and J. Found.). 

To study its mode of inhibition, we prepared several derivatives and measured their kinetics of inhibition. Both N-acetyl-statine and N-acetyl-alanyl-statine are competitive inhibitors for pepsin with values of 1.2 X lO M and 5.65 x 10 M, respectively. The value for N-acetyl-valyl-statine is 4.8 x 10 M. These statyl derivatives, therefore, are very strong inhibitors. The value for N-acetyl-statine is 600-fold smaller than that of its structural analog N-acetyl-leucine. The derivative which contains two statyl residues in a tetrapeptide exhibits inhibitory properties which approach those of pepstatin itself. Other acid proteases, human pepsin, human gastricsin, renin, cathepsin D, the acid protease from R. chinensis and bovine chymosin, also are inhibited by pepstatin and its derivatives. We suggest that the statyl residue is responsible for the unusual inhibitory capability of pepstatin and that statine is an analog of the previously proposed transition state for catalysis by pepsin and other acid proteases. 

P. Sepulveda and J. Tang, Oklahoma Medical Research Foundation, Oklahoma City, Partial Sequences of Human Pepsin and Gastricsin . 

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