Gastricsin

AA A1 A01.003 Gastricsin Polymorphism correlates with gastric ulceration... 

Aspartic proteases include the gastric proteases pepsin A, pepsin B, gastricsin and chymosin that are secreted as inactive zymogens and are activated through removal of autoinhibitory domains in the low pH conditions of the stomach [7-9]. Oesophagitis is caused by undue... 

Vertebrates pepsins and gastricsin chymosin = rennin Cathepsins, D, E Fungi... 

Amino Acid Compositions. Amino acid compositions of mammalian pepsinogen and pepsin, gastricsin, and prochymosin and chymosin have been collected by Fruton (46), Those of five fungal enzymes have been collected by Matsubara and Feder (29). 

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. 

It is now well known that the mammalian enzymes pepsin, gastricsin, and chymosin are secreted by the respective organisms as zymogens which are activated by the removal of over 40 residues from the N-terminal end. 

On starch gel electrophoresis, gastricsin migrated 6.5 cm toward the anode after 22 hours as one single narrow band in acetate buffer of pH 5.0. These two materials also differed in heat sensitivity while pepsin at pH 2.0 and 65° C lost 69% of its activity, gastricsin under these conditions lost 44.8%. Conversely, at pH 3.2 pepsin was inactivated only 11.2%, while gastricsin was inactivated 22.3% (Fig. 4). Both enzymes hydrolyzed synthetic carbobenzoxy-glutamyl-L-tyrosine, which is a specific substrate for pepsin. Gastricsin was crystallized as it came from... 

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).

Taylor (T24) repeated some of Tang s experiments. Materials eluted from an Amberlite IRC-50 column at pH 4.4, by the latter s method and corresponding to his gastricsin, exerted proteolytic activity with two maxima one near pH 2 and the other near pH 3.3. 

The basic controversy now revolves around the problem of the existence of a separate pepsin active at pH 1.5-2.0 and a separate gastric cathepsin (gastricsin) active at pH 3.2-3.5. The alternative concept is that the activity at pH 1.5-2.0 and at 3.2-3.5 belongs to a similar protease (pepsin), with the difference that one is derived from the ftmdic glands (fundic pepsin) and the other from the pyloric glands and perhaps chief neck cells (pyloric pepsin) (T22, T24). 

R6. Richmond, V., Tang, J., Wolf, S., Trucco, R. E., and Caputto, R., Chromatographic isolation of gastricsin, the proteolytic enzyme from gastric juice with pH optimum 3.2. Biochim. Biophys. Acta 29, 453-454 (1958). 

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