Pancreatic enzymes trypsin

The mammalian serine proteases have a common tertiary structure as well as a common function. The enzymes are so called because they have a uniquely reactive serine residue that reacts irreversibly with organophosphates such as diisopropyl fluorophosphate. The major pancreatic enzymes—trypsin, chymotrypsin, and elastase—are kinetically very similar, catalyzing the hydrolysis of peptides... 

Enzyme inhibitors of a protein nature are of significant concern because of widespread occurrence. The most common of these affect the pancreatic enzymes, trypsin and chymotrypsin. and arc found in legumes, as well as in egg whites and potatoes. 

In Table II are shown the results from kinetic studies with commercially available gastric and pancreatic enzymes. Trypsin was strongly inhibited, at least at a low concentration of casein as substrate. The hydrolysis of benzoyl arginine ethyl ester (BAEE) by trypsin was non-competitively inhibited, giving a 30% reduction of Vmax at 0.5 mg/ml of the LMW fraction. Carboxypepti-dase A, and to a lesser extent carboxypeptidase B, were non-competitively inhibited as well. Pepsin and chymotrypsin were not affected by the conditions used in these assays. 

No. It is metabolized in the duodenum by pancreatic enzymes (trypsin and chymotrypsin). 

An in vivo test for the assessment of pancreatic function which consists of giving secretin (which stimulates pancreatic bicarbonate production) and cholecystokinin-pancreozymin (which stimulates the secretion of pancreatic enzymes). Pancreatic fluid is collected and analysed for bicarbonate and one of the pancreatic enzymes (trypsin, amylase or lipase). Low outputs occur in pancreatic disease. 

Some of the pancreatic enzymes in the lumen include pancreatic amylase, pancreatic lipase, elastase, trypsin, a-chymotrypsin, and carboxypeptidase A. For example, the aspirin derivatives aspirin phenylalanine ethyl ester, aspirin phenyllactic ethyl ester, and aspirin phenylalanine amide have been studied as substrates for carboxypeptidase A [67,68], with the phenylalanine ethyl ester derivative proving to be the best substrate. This study indicated that the carboxypeptidase A may serve as a reconversion site for many drug derivatives. 

Release of active pancreatic enzymes directly causes local or distant tissue damage. Trypsin digests cell membranes and leads to the activation of other pancreatic enzymes. Lipase damages fat cells, producing noxious substances that cause further pancreatic and peripancreatic injury. 

Most patients with malabsorption require pancreatic enzyme supplementation (Fig. 28-2). The combination of pancreatic enzymes (lipase, amylase, and protease) and a reduction in dietary fat (to less than 25 g/meal) enhances nutritional status and reduces steatorrhea. An initial dose containing about 30,000 international units of lipase and 10,000 international units of trypsin should be given with each meal. 

The presence or absence of pancreatic enzymes can only be satisfactorily decided by intraduodenal intubation and direct examination of samples of small intestinal contents after the administration of a suitable stimulus to pancreatic secretion (Fll). It is not sufficient to look at one enzyme only, such as trypsin, since a specific deficiency of lipase can occur (Sll). Assessment of the degree of hydrolysis of fat in the stools is quite unreliable as a guide to pancreatic enzyme activity (CIO). 

For example, chymotrypsin cleaves peptides on the C-terminal side of aromatic amino acid residues phenylalanine, tyrosine, and tryptophan, and to a lesser extent some other residues with bulky side-chains, e.g. Leu, Met, Asn, Gin. On the other hand, trypsin cleaves peptides on the C-terminal side of the basic residues arginine and lysine. Elastase usually catalyses hydrolysis of peptide bonds on the C-terminal side of neutral aliphatic amino acids, especially glycine or alanine. These three pancreatic enzymes are about 40% identical in their amino acid sequences, and their catalytic mechanisms are nearly identical. 

These agents are administered to aid in the digestion of food. The primary digestant preparations contain pancreatic enzymes or bile salts. Pancreatic enzymes such as amylase, trypsin, and lipase are responsible for digestion of carbohydrates, proteins, and lipids, respectively. These enzymes are normally synthesized in the pancreas and secreted into the duodenum via the pancreatic duct. Bile salts are synthesized in the liver, stored in the gallbladder, and released into the duodenum via the common bile duct. Bile salts serve to emulsify lipids in the intestinal tract and are important in lipid digestion and absorption. 

Proteolysis of peptides and proteins commences in the stomach when pepsin is present. As a result, protein or peptide drugs will be hydrolyzed into smaller fragments like amino acids or oligopeptides, which are absorbed through the mucosa either by diffusion or by a carrier-mediated transport [18], In an average individual, 94-98% of the total protein is completely digested and absorbed [19], Proteolysis continues in the intestine with pancreatic enzymes like trypsine and brush-border enzymes. 

The pancreatic enzyme it stored and secreted as a proenzyme with an additional seven residues at the N-tcmiinus, The proenzyme serves, like the other pancreatic proteinase zymogens, to prevent aotodigestion of the pancreatic cells. Upon secretion into the gastrointestinal tract, trypsin cleaves off these seven residues to produce the enzymatic form with full activity on insoluble substrates. On monomeric substrates, however, there is little difference between the catalytic activity of the proenzyme and of the activated enzyme [34],... 

Pancreatic enzymes, preferably trypsin, have been used for the chemical characterisation and identification of many known bioactive peptides. For example, ACE-inhibitory peptides as well as CPPs are most commonly produced by trypsin (Maruyama and Suzuki, 1982 Berrocal et al., 1989). On the other hand, other enzymes and different enzyme combinations of proteinases, including alcalase, chymotrypsin, pancreatin and pepsin, as well as enzymes from bacterial and fungal sources have also been utilised to generate bioactive peptides. Higher yields of CPPs and, particularly, higher amounts of asl-casein f(59-79) in the hydrolysate have been obtained with casein micelles successively digested with pepsin and trypsin... 

Figure 26-2. The pancreatic enzyme cascade. Pancreatic proteases enter the intestinal lumen as inactive zymogens. Within the duodenum, a specific enzyme of the duodenal mucosa, enterokinase, activates trypsinogen by releasing the trypsinogen activation peptide (TAP). Subsequently, active trypsin activates the other zymogens and acts autocat-alytically.

Three of the four pancreatic proteases (trypsin, chymotrypsin, and elastase) are called serine proteases because they are all dependent for activity on the side chain of a serine residue in the active site. This serine residue attacks the carbonyl group of the peptide bond to cleave the peptide, giving an acyl-enzyme intermediate (Chap. 8). This ester bond is then hydrolyzed in a second step ... 

This group includes the chymotrypsins, trypsin, elastase, thrombin, and subtilisin. The name of this group of enzymes refers to the seryl residue that is involved in the active site. As a consequence, all of these enzymes are inhibited by diisopropylphosphorofluori-date, which reacts with the hydroxyl group of the seryl residue. They also have an imidazole group as part of the active site and they are all endopeptides. The chymotrypsins, trypsin and elastase, are pancreatic enzymes that carry out their function in the intestinal... 

The pancreas of all mammals so far investigated contain an elastase with similar enzymatic reactions (Lewis et al., 1956 Marrama et al., 1959), but immunological differences have been observed between pancreatic elastases from different species (Moon and Mclvor, 1960). Elastase is secreted in the pancreatic juice as an inactive zymogen, proelastase (Grant and Robbins, 1955 Lamy and Lansing, 1961) which, like other pancreatic enzymes, is activated by trypsin or enterokinase. 

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