Pepsin, precursor

The proteases are secreted as inactive zymogens the active site of the enzyme is masked by a small region of its peptide chain, which is removed by hydrolysis of a specific peptide bond. Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells trypsin can then activate chymotrypsinogen to chymotrypsin, proelas-tase to elastase, procarboxypeptidase to carboxypepti-dase, and proaminopeptidase to aminopeptidase. 

Pepsinogen is produced by the chief cells. Within the lumen of the stomach, this precursor molecule is split by HCl to form the active enzyme pepsin. Optimally active at an acidic pH (pH = 2), pepsin begins protein digestion by fragmenting proteins into smaller peptide chains. 

The activation of pepsin from its zymogen pepsinogen occurs by a different mechanism. In this case, the pH of the environment plays a decisive role. In the strongly acidic milieu of the stomach cleavage of a 44 amino acid peptide occurs from the inactive precursor pepsinogen. The activation is intramolecular and depends on the pH of the solution. 

Bovine haemoglobin, the protein from erythrocytes which occurs as a minor component in meat and meat products, is also a precursor of opioid peptides (haemorphins). These opioid peptides are released by pepsin digestion in vitro and may also be produced by macrophages. Moreover, haemorphins have been found to decrease the tension of the guinea pig ileum in vitro (Nyberg et al., 1997). 

Pepsinogen is secreted by chief cells in the gastric mucosa and is the precursor of the protease enzyme pepsin. 

Activation of a zymogen. Some enzymes are secreted as inactive precursors, called zymogens. Trypsin and pepsin are two such examples a portion of the zymogen must be cleaved off to form the active enzyme. Again, an on/ off switch more than a tight, variable regulation. 

The precursor of pepsin is pepsinogen (MW 40,000) and is converted into active pepsin in the gastric juice by the enzymatic action of pepsin itself. In this conversion, 42 amino acid residues are removed from the amino-terminal end of the polypeptide chain. The portion of the molecule that remains intact is enzymatically active pepsin of molecular weight 33,000 Dalton. Pepsin hydrolyses proteins at peptide bonds on the amino terminal side of tyrosine, phenylalanine and tryptophan and converts it into a mixture of smaller peptides. 

Gastric juice contains a mixture of water, inorganic ions, hydrochloric acid, pepsinogens, mucus, various polypeptides, and the intrinsic factor. Pepsinogens are precursors of the proteolytic enzymes, pepsins. They are readily converted into the corresponding pepsins by either acid or pepsin itself. Conversion... 

If the molecular weights of pepsin and pepsinogen are 35,000 and 38,000, respectively (61), each of these molecules contains one atom of phosphorus (28, 60). Since it had been shown that ovalbumin and a-casein are readily dephosphorylated by certain phosphatases from mammalian tissue, and from potato, the action of these enzymes on pepsin and its precursor w as studied. It was found that only the potato phosphatase at pH 5.6 de-phosphorylates pepsin and pepsinogen, whereas prostate phosphatase does not act on these proteins. The intestinal enzyme, although not active at pH 6.0, liberates phosphorus at pH 8.9 (67). 

If, as is shown in Table VII, these phosphorus-free proteins are then assayed for proteolytic activity, no loss is found when tested either with hemoglobin (4) or with the synthetic dipeptide, acetyl-L-phenylalanyl di-iodotjTosine (7) as a substrate. This indicates that the phosphorus in these proteins is unessential both for the enzymatic activity of pepsin and for the activation of the precursor, pepsinogen. 

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. 

Alzheimer s disease is characterized by plaques in the brain consisting primarily of the 40-42 amino acid amyloid / -peptide (A/ ) [258]. AfS derives from proteolysis of the amyloid precursor protein (APP) by the fS and y sec-retases to create the N and C-termini of the peptide respectively [259]. The / -secretase has recently been identified as a 501 amino-acid transmembrane protein by several research groups [260-263], The enzyme, variously named BACE, memapsin2, and Asp2, is an aspartic protease related to pepsin, cathepsin D, and renin, with all the properties expected of the /i-sccrctasc. 

Pepsinogen. This precursor of the proteolytic enzyme pepsin is secreted by gastric parietal cells pepsinogen activities may be increased following peptic ulceration and by parasitic infections. The enzyme may be measured in plasma or gastric fluid using colorimetric, fluorimetric, or radioimmunometric methods and ELISA methods (Will et al. 1984 Ford et al. 1985 Tani et al. 1987 Lynch et al. 2004). 

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. 

Complexes of oxidized lipids with proteins are cleaved with proteolytic enzymes, snch as pepsin, trypsin, or chymotrypsin, only slowly and incompletely thus, their consumption may give rise to digestion problems. In the past two decades, they have received great attention in hnman medicine because they are precursors of atherosclerotic plaques (Kromhout, 1999). 

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