Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total protein, alpha1-antitrypsin, alpha2-macroglobulin, amylase, methemalbumin, tryptic amidase activity, radioimmunoassayable elastase 2, and three lysosomal hydrolases were determined in the ascites fluid from patients with acute pancreatitis. In eight patients methemalbumin was detected in ascites and serum, supporting the diagnosis of hemorrhagic pancreatitis. Significant levels (4-45 microgram/ml) of tryptic amidase activity were detected in ascites samples from all patients. Evidence is presented which demonstrates that the tryptic amidase activity is due to alpha2-macroglobulin-bound trypsin. Pancreatic elastase 2, determined with a new sensitive and specific radioimmunoassay, ranged from 400 to 2100 ng/ml in serum and from 650 to 4460 ng/ml in ascites fluid. Substantial amounts of alpha2-macroglobulin-bound trypsin and elastase 2, entering the circulation from the peritoneal cavity, might be responsible for certain serious complications seen in acute pancreatitis. However, with the exception of serum calcium and methemalbumin and the ascites fluid methemalbumin and total protein, none of the biochemical parameters studied showed a distinct correlation with the patient's outcome.
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PMID:Studies on the ascites fluid of acute pancreatitis in man. 62 83

The peritoneal exudate formed during experimental pancreatitis is toxic when administered intraperitoneally or intravenously to other animals. Overwhelming of the peritoneal antiprotease defences by proteolytic enzymes released from the pancreas may be a key factor responsible for this toxicity and is examined in the current study. Human pancreatitis exudates possessed tryptic amidase activity indicating trypsinogen activation. The trypsin inhibitory capacities of exudates were reduced indicating a degree of consumption of the peritoneal antiproteases. Of 21 exudates examined, three showed marked reduction of their trypsin inhibitory capacity indicating almost complete consumption of their antiproteases. All three patients were shocked at the time of sampling, two dying of fulminant pancreatitis within 24 h. Overwhelming of the peritoneal antiproteases was not confirmed, but may occur in a few instances where proteolytic enzyme release or zymogen activation continues. Intraperitoneal administration of exogenous antiproteases prolongs survival in rats with pancreatitis and has been suggested as a therapy in man. The current data suggests that few patients are likely to benefit from such an approach.
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PMID:Role of the protease-antiprotease balance in peritoneal exudate during acute pancreatitis. 170 61

Activation of trypsinogen in acute pancreatitis results in subsequent increases in plasma levels of trypsin bound to the inhibitors alpha 1-protease inhibitor (alpha 1-PI) and alpha-macroglobulin (alpha-M). It seems logical to speculate that plasma levels of these inhibitor-bound forms of trypsin may reflect the degree of intrapancreatic zymogen activation and that determination of such parameters may be of diagnostic and prognostic value. In order to test this hypothesis, the concentrations of trypsinogen and of trypsin bound to alpha 1-PI have been determined in serial plasma samples from rats who died (N = 7) and survived (N = 5) following induction of pancreatitis with taurocholate. Since the other major reaction product of active trypsin in plasma, alpha-macroglobulin-bound trypsin, cannot be measured directly, the plasma levels of trypsin-like amidase activity were determined to estimate the concentration of trypsin-alpha-M complex. Shortly after induction of pancreatitis, elevated levels of trypsinogen were present in plasma, but no alpha 1-PI-bound trypsin could be detected. Trypsin-alpha 1-PI complex continuously increased over the time course of pancreatitis in animals that died. In contrast, the plasma levels of trypsin-alpha 1-PI complex were lower in animals that survived, peaked around 15 hr postinduction at levels (182 +/- 53 ng/ml) significantly lower than those in dying animals (543 +/- 346 ng/ml), and fell during the following 48 hr. There was a significant correlation between plasma trypsin-like amidase activity and plasma alpha 1-PI-bound trypsin. Our data demonstrate that the concentration of activated forms of plasma trypsin in the bloodstream are correlated with mortality in experimental pancreatitis.
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PMID:Correlation of trypsin-plasma inhibitor complexes with mortality in experimental pancreatitis in rats. 348 85

The levels of pancreatic digestive enzymes, lysosomal hydrolases, and protease inhibitors were evaluated in ascites fluid from 24 patients with acute pancreatitis diagnosed as alcoholic, gallstone-induced, or idiopathic. In this group the concentrations of amylase (354 +/- 98 ng/ml), immunoreactive cationic trypsinogen (1840 +/- 238 ng/ml), and immunoreactive elastase 2 (1492 +/- 262 ng/ml) were greatly elevated in comparison to the corresponding serum values. Enzyme levels in ascites from the idiopathic pancreatitis group tended to be higher than the levels from the other two groups. Activity of acid phosphatase and beta-glucuronidase was significantly higher in ascites compared to serum in all groups. On the other hand, levels of immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin in ascites fluid were about half the average concentrations reported for normal serum. Significant amounts of tryptic amidase activity (61.7 +/- 13.7 micrograms/ml) were observed, indicating a trypsin-alpha 2-macroglobulin complex. These data indicate an imbalance in the protease-to-inhibitor ratio in ascites fluid from patients with acute pancreatitis. Coupled with elevated ribonuclease activity (27.4 +/- 3.4 units), a positive methemalbumin test in 23 of 24 patients (1.1 +/- 0.4 mg hematin/100 ml), and an average protein concentration of 4.0 +/- 0.2 g/100 ml, these observations demonstrate that abdominal paracentesis and the biochemical analyses of ascites fluid provide useful information related to the biochemical events in acute pancreatitis and may be useful in the diagnosis of difficult cases, but their predictive value of severity remains to be established.
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PMID:Biochemical studies in peritoneal fluid from patients with acute pancreatitis. Relationship to etiology. 381 84

A canine model of bile-induced pancreatitis has been employed to investigate time-dependent changes in the molecular forms of trypsin in blood and ascitic fluid in this disease. The distribution of immunoreactive trypsin as trypsinogen and trypsin bound to plasma inhibitors in ascitic fluid and plasma during the course of the disease has been investigated by means of a radioimmunoassay for canine pancreatic cationic trypsin. In addition, trypsinlike amidase activity was determined in plasma and ascitic fluid using Z-Gly-Gly-Arg-beta-Nap as substrate. Early plasma and ascitic fluid samples in four dogs that died contained primarily trypsinogen, while extensive activation of trypsinogen to alpha 2-macroglobulin and alpha 1-protease inhibitor-bound trypsin occurred in the course of the disease. A fifth dog survived and showed little activation of trypsinogen. In the four dogs that died, the levels of trypsinlike amidase activity in the ascitic fluid were substantial throughout the course of the disease. The plasma levels of trypsinlike activity in these animals were much lower, but increased during the disease process. The dog that survived had lower concentrations of trypsinlike activity in ascitic fluid and plasma. These results suggest that activation of trypsinogen resulting in inhibitor-bound forms of trypsin in ascitic fluid and plasma is important in the pathogenesis of acute pancreatitis.
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PMID:Immunoreactive forms of cationic trypsin in plasma and ascitic fluid of dogs in experimental pancreatitis. 617 Feb 31

In previous studies of human and experimental acute pancreatitis, three main assumptions have been made. First, that the disease is due to activation of pancreatic proteolytic enzymes in the pancreas with resulting "autodigestion" of the gland. Second, that interstitial pancreatitis is a mild form of hemorrhagic pancreatitis into which it may progress, and third, that bacteria play little part, if any, in the initiation of the disease. These assumptions are now questioned. In the present study in dogs, levels of proteolytic enzymes in blood, thoracicduct lymph and peritoneal fluid were measured using benzoylarginine amide. Raised levels of amidase were found in hemorrhagic, but not with interstitial, pancreatitis, and biochemical examination of amidase suggested it was not a pancreatic protease, but with its broad specificity and stability derived from bacteria. Addition of antibiotic to the blind duodenal loop in hemorrhagic pancreatitis reduced the level of blood amidase, but Trasylol given intravenously did not, nor did it inhibit amidase in vitro. In all animals, histological examination was made of the pancreas at time of death. On bacteriology, it is concluded that experimental interstitial pancreatitis results from damage to the pancreatic duct system without infection, and haemorrhagic pancreatitis mainly from reflux of bacteria into the pancreatic ducts from the duodenum. Only bacteria such as Escherichia coli and Clostridium welchii that produce proteolytic enzymes and cytotoxins appear to be able to cause haemorrhagic pancreatitis, and these bacteria may explain the release of vasoactive polypeptides and the vascular effects. In hemorrhagic pancreatitis such bacteria were found in the pancreas, but none in interstitial pancreatitis. Evidence is given to suggest that pancreatic proteolytic enzymes are unlikely to cause the cell necrosis which is a pathological feature of hemorrhagic pancreatitis, and that "autodigestion" is likewise unlikely to be a cause of this condition. An extrapancreatic source of proteolytic enzymes from bacteria is now suggested in haemorrhagic pancreatitis, and more attention to bacteriology in human acute pancreatitis is urgently needed. Amidase levels were highest in peritoneal fluid, suggesting a rationale for peritoneal lavage in the treatment of acute pancreatitis, and it is unlikely that Trasylol can give any benefit. The assessment of treatment of acute pancreatitis will be unsatisfactory as long as the proportion of haemorrhagic to interstitial pancreatitis in any series is not known accurately.
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PMID:A nonpancreatic source of the proteolytic-enzyme amidase and bacteriology in experimental acute pancreatitis. 698 58