Trypsinogen-activating peptide

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). 

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.

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. 

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... 

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... 

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... 

Aspartate aminotransferase from pig heart mitochondria shows 48% homology with the cytoplasmic enzyme. Two human trypsinogens (I and II, I being the major form) differ in the activation peptides released. Oliviera et have reported the complete sequence of human C-reactive protein, and together with others have commented on the homology between this protein and human IgG. 

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. 

Proteolysis cleavage of peptide bonds to remodel proteins and activate them (ptoin-sulin, trypsinogen, prothrombinj... 

Protein digestion occurs in two stages endopeptidases catalyse the hydrolysis of peptide bonds within the protein molecule to form peptides, and the peptides are hydrolysed to form the amino acids by exopeptidases and dipeptidases. Enteropeptidase initiates pro-enzyme activation in the small intestine by catalysing the conversion of trypsinogen into trypsin. Trypsin is able to achieve further activation of trypsinogen, i.e. an autocatalytic process, and also activates chymotrypsinogen and pro-elastase, by the selective hydro-... 

In trypsinogen, a region of the protein at the binding pocket is disordered, indicating conformational flexibility.133,134 On activation or on the addition of a small peptide that can bind to the buried Asp-194, this region takes on a well-defined structure. 

The inactive precursors are called trypsinogen, pepsinogen, chymotrypsino-gen, and procarboxypeptidase. These precursors are converted to the active enzymes by hydrolytic cleavage of a few specific peptide bonds under the influence of other enzymes (trypsin, for example, converts chymotrypsinogen to chymotrypsin). The digestive enzymes do not appear to self-destruct, probably because they are so constructed that it is sterically impossible to fit a part of one enzyme molecule into the active site of another. In this connection, it is significant that chymotrypsin attacks denatured proteins more rapidly than natural proteins with their compact structures of precisely folded chains. 

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