Trypsinogen, activation

Trypsinogen-Activating Peptide (TAP). The most reliable way to assess trypsinogen activation is to measure trypsinogen-activation peptide (TAP) in serum, urine, pancreatic tissue, or ascitic fluid (H5, M4). Studies on TAP in... 

N3. Neoptolemos, J., Kemppainen, E., Mayer, J., Fitzpatric, J., Raraty, M., and Slavin, J., Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide A multicentre study. Lancet 255, 1955-1960 (2000). 

T3. Tenner, S., Fernandez-del Castillo, C., Washaw, A., Steinberg, W., Hermon-Taylor, J., and Valenzuela, J. E., Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis. Int. J. Pancreatol. 21,105-110 (1997). 

The Third Active Site Residue of Aspartic Proteinase from Aspergill us is Essential for Trypsinogen Activation... 

For trypsinogen activation, enteropeptidase (enterokinase, EC 3.4.21.9) [23] is a key enzyme for mammalian protein digestion. The selective cleavage site of trypsinogen by enteropeptidase initiates Lys6-Ile7 bond. Then trypsin (EC 3.4.21.4) activates other zymogens. Thus, the formation of trypsin by enteropeptidase is the master activation step. 

Figure 2. Activities of trypsinogen activation of the mutated D76S-aspergillopepsinI and aspergillopepsin I.

Thus, we concluded that Asp76 is the binding site for the basic substrate, trypsinogen, and that a single amino acid mutation (Asp76 —> Ser76) is sufficient to alter the substrate specificity of the enzyme for trypsinogen activation [29],... 

To probe the effects of the mutations on specificity at the Pi position, we used peptide substrates, Pro-Thr-Glu-Phe-Phe(4-N02)-Arg-Leu (PTEFF(4-N02)RL, peptide A ), Pro-Thr-Glu-Lys-Phe(4-N02)-Arg-Leu (PTEKF(4-N02)RL, peptide B ), and Ac-Ala-Ala-Lys-Phe(4-N02)-Ala-Ala-amide (Ac-AAKF(4-N02)AA-NH2, peptide C ). Peptide A was cleaved Phe-Phe(4-N02) bond, which represents pepsin-like activity, and peptide B and peptide C were cleaved at the Lys-Phe(4-N02) bond, which is equivalent to trypsinogen activation. No other bond in these peptides was hydrolyzed by any of the enzymes. From kinetic determination of... 

Casein (katal/kg) Hemoglobin (katal/kg) Trypsinogen activation (katal/kg)... 

Aorsin from Aspergillus Oryzae, a Novel Serine Proteinase with Trypsinogen Activating Specificity... 

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.

Question How are zymogens other than trypsinogen activated ... 

Fig. 6. Activation of chymotrypsinogen(s) and trypsinogen as a function of added trypsin (22). On the left chymotrypsinogen(s) activation in pig juice. Incubation time, 120 min. The other conditions are the same as in Fig. 5. On the right trypsinogen activation in pig juice. Incubation time, 18 hr. Abscissas, milligrams of added trypsin per 100 mg of total protein. Ordinates, specific activity (/i-equivalents/ min/mg of protein) after deduction of the activity of added trypsin.

Bovine trypsin can also be chromatographed on CM-cellulose at pH 3.2 in an ionic strength gradient (115). In this way, active trypsin begins to separate from inactive proteins present in commercial preparations or formed during trypsinogen activation in the absence of calcium. After... 

In the case of trypsinogen activation was obtained in the presence of catalytic amounts of trypsin. 

When trypsinogens are converted to active TRY, a small peptide is cleaved from the N-terminal region of trypsino-gen (trypsinogen activation peptide or TAP). Determinations of urinary TAP seem to provide useful information on the severity of acute pancreatitis,... 

Schmidt, J., E. Ryschich, H. P. Sinn, S. Maksan, C. Herfarth, and E. Klar. 1999. Trypsinogen activation peptides (TAP) in peritoneal fluid as predictors of late histopathologic injury in necrotizing pancreatitis of the rat. Digestive Diseases and Sciences 44 823-829. 

The pancreas synthesizes and stores the zymogens in secretory granules. The pancreas also synthesizes a secretory trypsin inhibitor. The need for the inhibitor is to block any trypsin activity that may occur from accidental trypsinogen activation. If the inhibitor were not present, trypsinogen activation would lead to the activation of all of the zymogens in the pancreas, which would lead to the digestion of intracellular pancreatic proteins. Such episodes can lead to pancreatitis. 

Specialized histochemical, immunohistochemical (IHC), and other tissue section-based molecular techniques (e.g., in situ hybridization (ISH)) can be used to better characterize the nature of the injury, cell types affected and its relationship to test article distribution and/or its intended target. The distribution of digestive enzymes or their proenzymes in the zymogen granules of acinar cells can be demonstrated using IHC markers for trypsin, chymotrypsin, carboxypeptidases A and B, lipase, amylase, elastase, DNase, and RNase (Cattley et al., 2013). Cytokeratin IHC markers can be used to differentiate epithelial components of the pancreas, most notably the cells of the ductal system. Amylase and MISTI have used been as IHC markers to confirm acinar cell differentiation experimentally. Trypsinogen activation peptide (TAP), a peptide released from trypsinogen when trypsin is activated, can be used as an IHC marker for intracellular activation... 

Exploratory Biomarkers Trypsin-Uke Immu-noreactivity, Pancreatic Lipase ImmunoreacHvity, and Trypsinogen Activation Peptides... 

TAP are small peptides that are released when trypsinogen is activated to trypsin. Under physiologic conditions, trypsinogen activation occurs in the intestinal lumen and is mediated by enteropeptidase. Within the intestinal brush border membranes, TAP is quickly degraded by peptidases. In AP, trypsinogen is prematurely activated within pancreatic acinar cells, and TAP is released into the peripheral circulation and potentially can be detected in serum and urine (Saez et al., 2005). Significant increases in plasma and/ or urine TAP concentrations have been reported in fehne, canine, and human patients with AP (Johnson et al., 2004). In humans, there is enough data in the hterature to show... 

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