Enzyme pepsin

The resuspended and formulated Fraction II precipitate normally contains some aggregated IgG and trace substances that can cause hypotensive reactions in patients, such as the enzyme prekail ikrein activator (186). These features restrict this type of product to intramuscular adininistration. Further processing is required if products suitable for intravenous adininistration are required. Processes used for this purpose include treatment at pH 4 with the enzyme pepsin [9001-75-6] being added if necessary (131,184), or further purification by ion-exchange chromatography (44). These and other methods have been fiiUy reviewed (45,185,187,188). Intravenous immunoglobulin products are usually suppHed in the freeze-dried state but a product stable in the solution state is also available (189). 

Oncolytic Enzymes. An early report of cancer chemotherapy using an enzyme, pepsin [9001 -75-6] was pubHshed in 1922 (18) its clinical use was surrounded by controversy. 

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 problem to be solved with respect to the chemical reactions that constitute metabolism and sustain life is that, without the action of catalysts, they are far too slow. Let s consider the digestion of the proteins themselves, an important constituent of our diet. In an enviromnent similar to that of our digestive system, several tens of thousand years would be required to digest half of the protein content of a typical meal in the absence of a catalyst. Clearly, this will not do. In reality, the stomach secretes one protein catalyst, the enzyme pepsin, and the pancreas secretes several enzymes that catalyze the digestion of proteins. In the presence of these enzymes, dietary proteins are fully digested and reduced to their basic constituents, the amino acids, in a matter of hours. Obviously, these enzymes are enormously potent catalysts." ... 

The use of enzymes for the manufacture of leather played a major role for the industrial scale production of enzymes. For the preparation of hides and skins for tanning, the early tanners kept the dehaired skins in a warm suspension of the dungs of dogs of birds. Wood was the first in 1898 to show that the bating action of the unpleasant dungs was caused by the enzymes (pepsin, trypsin, lipase) which they contained. In the context... 

FIGURE 2-21 The pH optima of some enzymes. Pepsin is a digestive enzyme secreted into gastric juice trypsin, a digestive enzyme that acts in the small intestine alkaline phosphatase of bone tissue, a hydrolytic enzyme thought to aid in bone mineralization. 

FIGURE 24.6 A computergenerated view of the enzyme pepsin, a typical globular protein. 

Lactobacillus GG enzymes + pepsin and trypsin (3-cn, asl-cn YPFP AVPYPQR TTMPLW Opioid, ACE-inhibitory, immunostimulatory Rokka et al. (1997)... 

The present study indicates that the extracellular enzyme, pepsin, exhibits striking differences from its mammalian homologue with respect to optimum pH, Ea for catalysis, thermal stability, and substrate affinity. These data are interesting from the viewpoint of biological adaption at low temperatures, but they also provide some substance to our contention that enzymes from fish plant wastes can have sufficiently unique properties to justify their use over conventional sources of enzymes used as food-processing aids. The relatively low Eas for protein hydrolysis by fish pepsins indicate they may be especially useful for protein modifications at low temperatures. Alternatively, the poor thermal stability of the fish pepsins studied indicate that the enzymes can be inactivated by relatively mild blanching temperatures. The reality of this concept will have to await studies where the pepsins are used as food-processing aids. Such studies are currently underway in our laboratory. 

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. 

The entry of protein into the stomach stimulates the release of a hormone, gastrin, which then causes the release of hydrochloric acid from the parietal cells, and pepsinogen from the chief cells (Fig. 15-5). Pepsinogen is another zymogen (they all start with pro- or end in -ogen) that is converted in the gastric juice to the active enzyme pepsin. 

The human stomach and small intestine also contain enzymes that help in the hydrolysis and break-down of proteins, first into shorter chain peptides (this is done with the aid of the enzymes pepsin and trypsin), and then hydrolysed further into individual amino acids with the help of the enzyme peptidase. Any fats in food are also hydrolysed in the stomach with the aid of lipase enzyme to form fatty acids (carboxylic acids). 

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

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. 

It is clear that a great deal of work is still required in the field of acid proteases before we reach the level of understanding attained for other groups of proteolytic enzymes. Fortunately the amino acid sequence work on at least three enzymes—pepsin, chymosin, and penicillopepsin— is well advanced, and complete three-dimensional structures should become available in the near future. A tentative structure for rhizopus-pepsin has been obtained, but in the absence of sufficient sequence information interpretation of the electron density maps is difficult. We can... 

Breakdown of ingested proteins occurs in the gastrointestinal tract by digestive enzymes pepsin from the stomach trypsin, chymotrypsin, and carboxypeptidase from the pancreas aminopeptidases and dipeptidases from the small intestinal wall. (Dipeptidases work on dipeptides. Aminopeptidase attacks the amino end of a peptide chain whereas carboxypeptidase attacks the carboxyl end of a peptide). Such digestion is certainly vital as 10 of the amino acids are essential, having to be acquired in the diet. 

The sulfate esters and sulfonate derivatives of polysaccharides and lignin form chemical complexes with the enzyme pepsin. These complexes have no proteolytic activity. Bc-cau.se polysulfatcs and polysulfonates arc ptxirly absorhol from the GI tract, specific chemical complexaiion appeals to be a desirable mechanism of pepsin inhibition. Unfoitu-nately. these polymers are also potent anticoagulants. 

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... 

Stadie, W. C., Riggs, B. C., and Haugaard, N., Oxygen poisoning. VI. The effect of high oxygen pressure upon enzymes pepsin, catalase, cholinesterase, and carbonic anhydrase. J. Biol. Chem. 161, 175-180 (1945). 

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