Pepsinogen concentration

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

The results of these experiments confirmed that, with a judicious choice of protein concentration and pH, first-order kinetics could be observed. This is verified by the linear semilog plots of pepsinogen concentration as a function of time, which are shown in Figure 1, and by the lack of dependence of the first-order rate constant on protein concentration, which is shown in Table I. 

At pH 4, the pepsinogen concentration versus time did not decline exponentially. Consequently, we assumed that both the first-order and autocatalytic activation mechanisms were operative. The rate equation for this reaction is ... 

Except for the enterochromaffin-like (ECL) cells, the density of the different cell types seemed to be mainly unchanged, indicating a balanced, harmonic growth of the different cell types. This is also supported by the finding in the rat that the pepsinogen concentration in the oxyntic hypertrophic mucosa was the same as in the normal control mucosa [2]. 

The stomach secretes pepsinogens, which are inactive proteolytic enzymes, and protons - the high concentration of which initiates hydrolysis of the pepsinogens to form active pepsins, which then continue their own activation, via an autocatalytic, hydrolysis (Appendix 4.1). 

In the diet, vitamin B12 is bound to proteins. Although some release of protein-bound vitamin B12 begins in the mouth, most of the release occurs in the stomach on exposure of food to gastric acid (HC1) and the proteolytic enzyme pepsin. For this reason, either hypo-chlorhydria (abnormally low concentration of HC1 in gastric fluid) or achlorhydria (the absence of HC1 in gastric fluid) may decrease the availability of dietary vitamin B12 for absorption by preventing the activation of pepsinogen to pepsin, the principal enzyme responsible for proteolysis in the stomach. Achlorhydric patients with adequate production of IF may have low normal or subnormal serum B12 concentrations because of failure to liberate B12 bound to food. 

Zymogen activation. When very low concentrations of pepsinogen are added to acidic media, how does the halftime for activation depend on zymogen concentration ... 

The presence of the highest concentration of pepsin on continuous electrophoresis was demonstrated by Wada et al. (W8) in the most anodic area of the electropherogram, while the minor peak of proteolytic activity had a less negative anodic charge (Fig. 10). In the anacid gastric juice, the proteolytic activity was localized more toward the middle of the partition, probably due to the presence of nonactivated pepsinogen in this area, having slower anodic mobility. 

In further studies, the authors (S7a, S7b) were able to concentrate and identify three distinct pepsinogens from human gastric mucosa by column... 

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. 

In addition to the decreased intestinal absorption of calcium in uremia, calcium ATPase activity is also low (S6). Many gastrointestinal hormones are found in increased concentrations in uremia. These include gastrin (OlO), cholecystokinin (OlO), pepsinogen I (II), gastric inhibitory peptide (LI), amylase, and trypsin (R17). There is a decrease in the conjugation of cholic to deoxycholic acid (G13) and in the pancreatic secretion of bicarbonate (Oil). Hepatic output of urea is decreased, as is the activity of some urea cycle enzymes e.g., ornithine tran-scarbamylase (T9). The clinical significance of these hormonal and enzymatic perturbations remains to be elucidated. 

In contrast, however, we have demonstrated that the macromolecular conformation of the zymogen differs markedly from that of the enzyme (17). Thus, if pepsinogen is transferred from an aqueous solution to concentrated urea, the specific rotation, [a]m, decreases from —200° to —320° in the concentration range of 1.5 to 4.0M urea, and the rotatory dispersion constant, Xc, decreases from 236 to 216 m/z. As shown in Figure 2, which also includes the results obtained with pepsin, this change reflects a configurational transition, similar in sharpness to the transition from an a-... 

Figure 4- Dependence of optical rotatory dispersion of pepsinogen and pepsin in far-ultraviolet on pH and urea concentration...

Figure 7. Dependence of potentiometric titration of pepsinogen in NaCl of various concentrations on temperature...

Pilotto A, Franceschi M, Lagni M) Fabrello R, Fortunate A, Meggiato T, Soffiati G, Oliani G, Di Mario F. The effect of omeprazole on serum concentrations of theophylline, pepsinogens A and C, and gastrin in elderly duodenal ulcer patients. Am J Ther (1995) 2, 43-6. 

SamlofFs electrophoretic method detected seven pepsinogens occurring at low concentration in the urine of normal subjects. The slowly moving protease was always absent. In 180 control subjects, Samloff found Pg 2 through Pg5 in 152 only Pg2, Pg3, and Pg4 occurred in the urine of others. 

The circular dichroism spectrum of the acid proteinase from Endothia parasitica was measured on a Cary61 CD spectrometer at 27 C, at a protein concentration of 0.232 mg/ml in 0.05 M phosphate buffer at pH 4.48. The path length was 10 mm for the near u.v. and 1 mm for the far u.v. The far u.v. circular dichroism is shown in Figure 6b. The spectrum resembles that of pepsin (21) and pepsinogen (22). The spectrum between 195 and 240 nm has been fitted using three sets of standard curves (23-25) with a least squares program (written by... 

The first kinetic study of pepsinogen activation was made by Herriott (6), who showed that pepsinogen is capable of spontaneous activation if it is subjected to an acidic pH of 6 or less. At pH 4.6, 25, an 8.75 mg/ml pepsinogen solution is half activated in about 6 hours. The observed data for pepsin concentration as a function of time fit an autocatalytic rate equation of the form ... 

Figure 1. Typical semilog plots of pepsinogen activation at different pH values. Protein concentration in all instances is 1 mg/ml.

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