Trypsinogen peptides

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-... 

Figure 12-12 Formation of the oxyanion hole following cleavage of trypsinogen between Lys 15 and He 16. (A) Stereoscopic view. (B) Schematic representation. The newly created terminal -NH3+ of He 16 forms a hydrogen-bonded ion pair with the carboxylate of Asp 194. This breaks the hydrogen bond between Asp 194 and His 40 in trypsinogen, inducing the peptide segment 192-194 to shift from an extended conformation to a helical form in which the NH groups of Gly 193 and Ser 195 form the oxyanion hole. Notice that the positions and interactions of Asp 102, His 57, and Ser 195, the catalytic triad, are very little changed. From Birktoft et al.270...

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. 

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). 

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... 

Many enzymes are synthesized as inactive zymogens and are activated only after secretion from their site of synthesis and storage. Activation is achieved by cleavage of one or more peptide bonds. A standard example is the secretion of trypsinogen and chymotrypsinogen from the pancreas into the gas-... 

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.

In the duodenum, the pancreatic zymogens, trypsinogen, chymotrypsinogen, proelastase and procarboxypeptidase are converted into active enzymes by enteropeptidase and trypsin, as shown in Fig. 15-6. The activation of all the zymogens involves cleavage of peptide bonds and removal of peptides, enabling conformational changes and formation of a functional active site. 

The oxidation of trypsin and trypsinogen was carried out in aqueous 0.1 M acetate buffer solutions at room temperature. In this particular case and under these conditions no significant cleavage of peptide bonds next to tryptophan residues occurred. Careful analysis of hydrolyzates of NBS-oxidized trypsinogen and trypsin confirmed the selectivity of the oxidative modification of the protein, as Table XXIV shows. There is no significant loss of tyrosine, histidine, serine, threonine, or cystine, although all of these amino acids will react with NBS but considerably less rapidly than tryptophan. 

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