Pepsinogen group

Alterations in other gastric secretions, such as pepsinogens and blood group substances also take place in chronic atrophic gastritis. The secretion of pepsinogen I has been used as an indicator of intestinal metaplasia and gastric cancer (21, 22). 

Pepsin Pepsinogen Stomach 42 amino acids HC1 and pepsin Amino group contributed by Tyr, Phe, Leu... 

Most dietary proteins are known not to be absorbed in humans as intact forms. Instead, they are usually broken down into amino acids or di- and tripeptides first in the GI tract. The stomach secretes pepsinogen, which is converted to the active protease pepsin by the action of acid. Pepsins, which are most active at pH 2-3, hydrolyze partially digested dietary proteins. The partially digested dietary proteins are further broken down by proteolytic enzymes (peptidases) produced by the pancreas and secreted in the duodenum of the small intestine. The peptidases that break the internal peptide linkages are known as endopeptidases, whereas those that attack the terminal, or end, groups of amino acids are called exopeptidases. 

The failure of the prostate enzyme to dephosphorylate pepsin and pepsinogen made it appear likely that the phosphate group in these proteins is not a monoester of the 0—type. Pretreatment of pepsin with a diesterase permits subsequent dephosphorylation with the prostatic enzyme, and it thus becomes clear that the phosphorus of this protein is present as a diester of the —O—P— 0— type. 

Protein digestion begins in the stomach, where protein is denatured by the low pH and is exposed to the action of pepsin. The low pH also provides the optimal H+ concentration for pepsin activity. The zymogen precursor pepsinogen (M.W. 40,000) is secreted by the chief cells and is converted to pepsin (M.W. 32,7(K)) in the acid medium by removal of a peptide consisting of 44 amino acid residues. This endopeptidase hydrolyzes peptide bonds that involve the carboxyl group of aromatic amino acid residues, leucine, methionine, and acidic residues (Table 12-5). The products consist of a mixture of oligopeptides. 

Ichinose, M., Miki, K., Furihata, C., Kageyama, T., Hayashi, R., Niwa, H., Oka, H., Matsushima, T., and Takahoshi, K., Radioimmunoassay of serum Group I and Group II pepsinogens in normal controls and patients with various disorders. Clin. Chim. Acta 126, 183-191 (1982). 

End group analyses of pepsinogen, a protein with a molecular weight of 40,000, revealed one AT-terminal amino acid, leucine, and one C-terminal amino acid, alanine (13,21). In contrast, pepsin of 35,000 molecular weight... 

In view of the fact that the number of basic amino acid residues in pepsinogen exceeds that present in pepsin, and these residues may function as conformational determinants, the dependence of the specific optical rotation, [a ]366, on the pH of the solution had to be considered. If the pH of the solution is altered from 6.5 to 11.5, the levorotation increases markedly in the pH range of 9.2 to 10.8 with the mid-point at pH 10.0. This value approximates the apparent pK of the -amino group of the lysyl residues if present in peptide linkage. 

What do these results indicate As shown earlier, pepsinogen contains an appreciable number of basic amino acid residues all clustered within a relatively small part of the molecule, whereas the acidic groups are distributed over the pepsin moiety. At neutral pH a significant number of acidic side chains are neutralized by the proximity of the -amino groups. Thus these charged side chains participate in some mutual interaction,... 

To sustain this view, two polypeptidyl pepsinogens were prepared by polymerization of the protein with the iV-carboxy-a-ainino acid anhydride of alanine and tyrosine, respectively ( ). Here the e-amino group with an apparent pK of 10.4 is replaced by an a-amino group of the amino acid attached, having the lower pK of 7.8. In another set of experiments pep-... 

To assess further the nature and the reactivity of the basic groups which contribute to the stabilization of pepsinogen, spectrophotometric... 

Pepsinogen is called a zymogen or inactive enzyme precursor, which is activated by the enzymatic action of trace amounts of pepsin already present in the stomach. Activation is achieved by the removal of a small terminal peptide. Pepsin attacks the peptide bonds of amino acids possessing hydrophobic side groups, which reduces proteins to mbttures of smaller peptides. Other enzymatic hydrolases which are found in the small intestine are also secreted as zymogens, and are activated by similar processing. 

Table 2-2. Mean Serunn Group I Pepsinogen Concentrations and Acid Output Arranged According to Diagnosis...

Source Adapted from Samloff IM, Secrist DM, Passaro E Jr. A study of the relationship between serum Group I pepsinogen levels and gastric acid secretion. Gastroenterology 69 1196-1200, 1975. 

Pure pepsin contains one atom of phosphorus per mole. Except for one phosphate group, the molecule is composed only of amino acid residues. The phosphate group has been removed from both pepsin and pepsinogen by certain phosphatases to yield proteins that retain proteolytic activity. Therefore, the phosphate group that gives pepsin its... 

Pepsinogen Pepsin Gastric mucosa Hydrochloric acid and autocatalysis Those in which Phe, TyrorTrp contribute the -NH-group 1-5-20... 

The enzymes are predominantly secreted in the fundus. The general proteolytic activity shows an optimum of about pH 1.8 to 2.2. Low activity towards hydrolysis of carbobenzoxy-tyrosyl-alanine and high activity towards acetyl-phenylalanyl-diiodotyrosine has been reported as characteristic for pepsin A (20). By electrophoresis at pH 8.5 for pepsinogen, or pH 5.0 to 5.4 for pepsin, this group of enzymes has the greatest mobility toward the anode (21-25). 

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