Pepsinogen carbohydrates

Gastric acid secretion is inhibited in the presence of acid itself. A negative feedback occurs when the pH approaches 2.5 such that further secretion of gastrin is inhibited until the pH rises. Ingested carbohydrates and fat also inhibit acid secretion after they reach the intestines several hormonal mediators for this effect have been proposed. The secretion of pepsinogen appears to parallel the secretion of H+, while the patterns of secretion of mucus and bicarbonate have not been well characterized. 

The first structure of human renin was obtained from prorenin produced by expression of its cDNA in transfected mammalian cells. Prorenin was cleaved in the laboratory to renin using the protease trypsin. Because the carbohydrates in renin are not required for bioactivity, oligosaccharides were removed enzymatically. This process facilitates crystallization in some cases and also removes the contribution of the heterogeneous sugar chains to the diffraction pattern. The structure was determined without the use of heavy-atom derivatives, by application of molecular replacement techniques based on the atomic coordinates of porcine pepsinogen as the model. The molecular dynamic method of refinement was used extensively to arrive at a 2.5 A resolution structure. However, some of the loop regions were not well resolved in this structure (Sielecki et al, 1989 Sail et al, 1990). 

Pspsin (EC 3.4.23.1) a protease in the stomach of all vertebrates with the exception of stomachless fish (e.g. carp). Purified P. shows maximal activity at pH 1-2, but in the stomach the optimal pH is 2-4. Above pH 6, P. is inactivated by denaturation. It preferentially catalyses hydrolysis of peptide bonds between two hydrophobic amino acids (Phe-Leu, Phe-Phe, Phe-TyrT With the exception of protamines, keratin, mucin, ovomucoid and other carbohydrate-rich proteins, most proteins are attacked by P. The products of P. action are peptone, i. e. mixtures of peptides in the M range 300-3,000. P. is a highly acidic (pi 1), single chain phosphoprotein (327 amino acid residues of known primary sequence, M, 34,500), which is released from its zymogen (pepsinogen, 42,500) by autocatalysis in the presence of hydrochloric acid. 

Pepsins and Pepsinogens.—The carbohydrate compositions and some sequences of amino-acids have been determined for glycopeptides derived from pepsinogens isolated from Japanese monkeys. Glycopeptides released by successive treatments of pepsinogen I with thermolysin and aminopeptidase contained 2-amino-... 

A content of carbohydrates is a theoretical possibility for heterogeneity in the gastric proteinases. Kageyama and Takahashi (37a) have shown that the carbohydrates are linked to an asparagine residue in the pepsin part of the monkey pepsinogen. At least two carbohydrate containing residues have been observed in the sequence of human pepsin (Sepulveda and Tang, personal communication). On the other hand, Stepanov (38) have reported that... 

It has been suggested that glucose is covalently bound to porcine pepsinogen but not pepsin (9) and, if this were so, the activation process might be affected by this carbohydrate. Consequently, carbohydrates have been analyzed by gas-liquid chromatography on pepsinogens from different species. 

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