Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are changes in both the plasma renin system and plasma kallikrein system during parturition. To investigate the interrelationship between plasma inactive renin and plasma kallikrein, we measured plasma active renin, inactive renin, active kallikrein and inactive kallikrein in 21 parturient women just before delivery and on the 5th day after delivery, and also in 30 newborn babies upon birth and on the 5th day after birth. Plasma active renin was measured by radioimmunoassay of angiotensin I generated after the addition of an exogenous substrate. Inactive renin was activated by trypsin. Active kallikrein was measured by kallikrein activity on substrate S-2302. Inactive kallikrein was activated by an activator containing the Hageman factor and kininogen. The results showed a significant decrease in active renin, inactive renin, and a significant increase in active kallikrein, inactive kallikrein and the active/total kallikrein ratio in mothers on the 5th day after delivery. In vaginally delivered babies, a decrease in active renin and in the active/total renin ratio were observed on the 5th day after birth, but inactive renin, active and inactive kallikrein showed no change. In babies delivered by cesarean section, no change in either the renin or kallikrein level was found. The patterns of change in plasma active renin and inactive renin in mothers and babies are in keeping with previous suggestions that plasma inactive renin is prorenin. There was no correlation between the plasma active/total renin ratio or the plasma active kallikrein level in mothers and babies, either before or after delivery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma renin and kallikrein in parturient women and newborn babies. 168 Oct 14

Tryptase from human mast cells has been shown (in vitro) to catalyze the destruction of fibrinogen and high-molecular-weight kininogen as well as the activation of C3a and collagenase. Although large amounts of tryptase are released in tissues by degranulating mast cells and levels as high as 1000 ng/ml have been measured in the circulation following systemic anaphylaxis, no specific physiologic inhibitor has yet been found for the protease. The current work tests several more inhibitors for their effects on tryptase and examines any effect of tryptase on these inhibitors. First, antileukoprotease and low-molecular-weight elastase inhibitor from human lung and hirudin and antithrombin III had no effect on tryptase activity in vitro. Second, the possibility that tryptase, being insensitive to the effects of inhibitors, might instead destroy them was also considered. Tryptase failed to cleave and inactivate antileukoprotease, low-molecular-weight elastase inhibitor, alpha 1 protease inhibitor, alpha 2 macroglobulin, and antithrombin III. Third, based on the knowledge that tryptase stability is regulated by its interaction with heparin, antithrombin III was used as a model heparin-binding protein to demonstrate that a protein competitor for heparin-binding sites, presumably by displacement of tryptase, destabilizes this enzyme. Conversely, tryptase, in excess, blocked the binding of antithrombin III to heparin, thereby attenuating the heparin-mediated inhibition of thrombin by antithrombin III.
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PMID:Interactions of human mast cell tryptase with biological protease inhibitors. 168 95

We discovered an enzyme in human platelets that deamidates substance P and other tachykinins. Because an amidated carboxyl terminus is important for biological activity, we purified and characterized this deamidase. The enzyme, released from human platelets by thrombin, was purified to homogeneity by ammonium sulfate precipitation, followed by chromatography on an octyl-Sepharose column and chromatofocusing on PBE 94. The purified enzyme exhibits esterase, peptidase, and deamidase activities. The peptidase activity (with furylacryloyl-Phe-Phe) is optimal at pH 5.0 while the esterase (benzoyl-tyrosine ethyl ester) and deamidase (D-Ala2-Leu5-enkephalinamide) activities are optimal at pH 7.0. With biologically important peptides, the enzyme acts both as a deamidase (substance P, neurokinin A, and eledoisin) and a carboxy-peptidase (with bradykinin, angiotensin I, substance P-free acid, oxytocin-free acid) at neutrality, although the carboxypeptidase action is faster at pH 5.5. Enkephalins, released upon deamidation of enkephalinamides, were not cleaved. Gly9-NH2 of oxytocin was released without deamidation. Peptides with a penultimate Arg residue were not hydrolyzed. Some properties of the deamidase are similar to those reported for cathepsin A. The deamidase is inhibited by diisopropylfluorophosphate, inhibitors of chymotrypsin-type enzymes, and mercury compounds while other inhibitors of catheptic enzymes, trypsin-like enzymes, and metalloproteases were ineffective. In gel filtration, the native enzyme has an Mr = 94,000 while in non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis the Mr = 52,000 indicating it exists as a dimer. After reduction, deamidase dissociates into two chains of Mr = 33,000 and 21,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. [3H]diisopropylfluorophosphate labeled the active site serine in the Mr = 33,000 chain. The first 25 amino acids of both chains were sequenced. They are identical with the sequences of the two chains of lysosomal "protective protein" which, in turn, has sequence similarity to the KEX1 gene product and carboxypeptidase Y of yeast. This protective protein complexes with beta-galactosidase and neuraminidase in lysosomes and is vitally important in maintaining their activity and stability. A defect in this protein is the cause of galactosialidosis, a severe genetic disorder. The ability of physiological stimuli (e.g. thrombin or collagen) to release the deamidase from platelets indicates that it may also be involved in the local metabolism of bioactive peptides.
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PMID:A peptidase in human platelets that deamidates tachykinins. Probable identity with the lysosomal "protective protein". 169 76

This study determines the release of nitric oxide (NO) from the coronary circulation of Langendorff hearts of rabbits, subsequent to administration of glyceryl trinitrate (GTN) and SIN-1. NO was measured on-line in the coronary effluent by the oxyhaemoglobin technique. Infusion of either GTN (10-40 mumoles/l) or SIN-1 (0.1-2.3 mumoles/l) into the coronary inflow resulted in a concentration-dependent NO release into the coronary effluent and a decrease in the coronary vascular resistance. NO generation from SIN-1 was identical with and without passage of the coronary circulation whereas NO generation from GTN was only detected after passage of the coronary vascular bed. NO generation by both substances was in the same range as endogenous NO release by two endothelium-dependent vasodilators, bradykinin (0.05 mumoles/l) and substance P (0.05 mumoles/l). Oxyhaemoglobin used for the assay of NO, inhibited the relaxation by SIN-1, but did not reduce vessel relaxations induced by GTN or iloprost, a stable prostacyclin analogue. Removal of the coronary endothelium by trypsin or pretreatment with L-NG-Monomethylarginine (30 mumoles/l) did neither affect NO release from GTN and SIN-1 nor the vasodilatory effect of both substances. These data are the first to directly demonstrate endothelium-independent NO release from organic nitrates during passage of an intact organ circulation. They additionally suggest a subendothelial site of metabolic NO formation from GTN.
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PMID:On-line measurement of nitric oxide release from organic nitrates in the intact coronary circulation. 171 35

T-kininogen, the major kininogen in rat plasma, releases Ile-Ser-bradykinin (T-kinin) when incubated with trypsin, but is not a substrate for tissue kallikrein. Enzymes able to release T-kinins from T-kininogen have been found in the rat submandibular gland, but precise identification of these enzymes and their possible relationship to kallikrein-like enzymes has not been established. We studied T-kininogenase activity in fractionated submandibular gland homogenate. The main T-kininogen catalytic enzyme was purified and characterized, and found to be identical to antigen gamma, a kallikrein-like enzyme which we have previously characterized. Of other identified kallikrein-like enzymes only tonin showed weak T-kininogenase activity, which was about 0.25% of that of antigen gamma. No other T-kininogen catalytic enzymes were observed. Antigen gamma released a kinin which was identified as T-kinin by reverse-phase h.p.l.c. The T-kininogenase activity of antigen gamma had a Km of 29 +/- 4 microM and a kcat/Km of 140 M-1.s-1, and was comparable with its high and low molecular mass-kininogenase activity (7.4 and 10 micrograms of kinin/h per mg respectively). In contrast, tissue kallikrein released 0.2 and 42,200 micrograms of kinin/h per mg respectively. Thus antigen gamma is a weak kininogenase. The isoelectric point of antigen gamma, but not its molecular mass, differed from that of other kallikrein-like enzymes. Isoelectrofocusing in flat-bed gels combined with immunostaining was therefore a convenient method for identification. The kallikrein-like nature of antigen gamma was demonstrated by its immunological similarity to tissue kallikrein and tonin and by 91% and 87% amino acid sequence similarity with tonin and kallikrein respectively (67 amino acids sequenced). Complete identity was also not observed with other sequenced kallikrein genes, mRNAs or proteins.
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PMID:T-kininogenase activity of the rat submandibular gland is predominantly due to the kallikrein-like serine protease antigen gamma. 174 46

The proteinase meprin-A is a disulfide-linked tetramer of 90-kDa glycoprotein subunits. It is expressed at high levels in kidney brush border membranes of random bred and certain inbred strains of mice. Some mouse strains (e.g. C3H/He) do not express meprin-A subunits, but do produce a similar but less well characterized metalloendopeptidase, meprin-B. In the present study, meprin-B was purified from C3H/He mouse kidneys to electrophoretic homogeneity, and the relationship between it and meprin-A was investigated. The papain-solubilized form of meprin-B was similar to meprin-A in amino acid composition, molecular mass, secondary, and quaternary structure. However, immunoblots indicated that the enzymes have some common and some distinct epitopes. Lectin blots indicated both enzymes have high mannose and/or complex biantennary oligosaccharides, but there are differences in the complex-type glycosylation. Peptide maps and sequencing of cyanogen-bromide fragments of the enzymes revealed some different amino acid sequences. Thermal inactivation studies indicated that meprin-B was much less stable than meprin-A; the half-life for inactivation at 58 degrees C for meprin-A was 50 min, whereas for meprin-B it was less than 3 min. Both enzymes hydrolyzed azocasein and insulin B chain, but limited proteolysis of the enzymes with trypsin activated meprin-B 5-20-fold, whereas meprin-A was activated 2-fold at most. Analysis of hydrolysis products of the oxidized insulin B chain revealed some common and some distinct sites of cleavage. Bradykinin was a good substrate for meprin-A, while it was not hydrolyzed by meprin-B. A synthetic peptide, YLVC(SO3-)GERG, derived from insulin B chain was hydrolyzed faster by meprin-B than meprin-A, and neither enzyme was activated by trypsin treatment against this substrate. Taken together, the data indicate that the two metalloendopeptidases have many similarities but are distinct enzymes.
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PMID:Meprin-A and -B. Cell surface endopeptidases of the mouse kidney. 189 22

High molecular weight kininogen (HKg) and T kininogen (TKg) were detected and localized by immunocytochemistry in adult rat hypothalamus. In addition, kininogens were measured by their direct radioimmunoassay (RIA) or by indirect estimation of kinins released after trypsin hydrolysis and high pressure liquid chromatography (HPLC) separation of bradykinin (BK) and T kinin. A specific HKg immunoreactivity demonstrated with antibodies directed against the light chain (LC) of HKg was colocated with SRIF in neurons of hypothalamic periventricular area (PVA) projecting to external zone (ZE) of median eminence (ME). Heavy chain (HC) immunoreactivity which could be related to HKg or to low molecular weight kininogen (LKg) was detected in some other systems: i) parvocellular neurons of suprachiasmatic (SCN) and arcuate nuclei containing SRIF, ii) magnocellular neurons (mostly oxytocinergic) of paraventricular (PVN) and supraoptic (SON) nuclei, iii) neurons of dorsomedian and lateral hypothalamic areas. TKg immunostaining was restricted to magnocellular neurons of PVN, SON, accessory nuclei (mostly vasopressinergic) and to parvocellular neurons of SCN (vasopressinergic). TKg projections are directed towards the internal zone (ZI) of ME, but very few immunoreactive terminals are detectable in neurohypophysis. TKg staining parallels with vasopressin during water deprivation, and is undetectable in homozygous Brattleboro rats. In some magnocellular neurons, TKg and HC (related to HKg or LKg) are coexpressed. TKg, was also detected in hypothalamus and cerebellum extracts by direct RIA, and BK and T kinin were identified after trypsin hydrolysis. HKg and LKg can act as precursor of BK which can play a physiological role as releasing factor, neuromodulator--neurotransmitter,--or modulator of local microcirculation in hypothalamus. The three kininogens are also potent thiolprotease inhibitors which could modulate both the maturation processes of peptidic hormones and their inactivation and catabolism.
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PMID:The kallikrein-kinin system in the rat hypothalamus. Immunohistochemical localization of high molecular weight kininogen and T kininogen in different neuronal systems. 191 78

Biochemical signs of pancreatitis in plasma and pancreatic exudates were determined in 22 pigs subjected to pancreatic allograft transplantation after the graft had been in cold storage for 6 hr. Two perfusion and preservation media were used. We found signs of protease activation in the pancreatic exudate during the first hour after reperfusion. The local protease protection barrier was, however, not broken and no plasma changes indicating pancreatitis were seen during this period. On the first and second postoperative days, mild biochemical signs of pancreatitis were seen in the plasma, including a decrease in kininogen and C3 concentration as well as in plasma kallikrein inhibitory activity and the appearance of trypsin-protease inhibitor complexes. No correlation was seen between these biochemical signs of pancreatitis and graft appearance or function, indicating that the reperfusion pancreatitis seen after 6 hr of cold storage is of minor significance. No significant differences were seen between the two preservation media used (Perfadex and EuroCollins solution).
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PMID:Biochemical characterization of reperfusion pancreatitis in porcine pancreatic allografts after six hours of cold storage. 201 26

Evidence for a kallikrein-kinin system (KKS) in fish is incomplete. In the present study, components of the KKS were identified in rainbow trout. Tissues were assayed for kallikrein-like esterolytic activity using three synthetic kallikrein substrates (TAME, VGAN, and PPAN), and the presence of kallikrein substrate (kininogen) in trout plasma was estimated by bradykinin (BK) radioimmunoassay of plasma activated with trypsin (T). Formation of pressor-depressor substances in vivo by porcine glandular kallikrein (GK) and T was measured after intra-arterial injection into unanesthetized trout. Gill and kidney contained kallikrein activity (TAME and VGAN assays); little activity was observed with PPAN. Aprotinin inhibited gill activity (TAME assay). T liberated 42 +/- 3 (SE) ng (n = 10) of immunoreactive BK per milliliter of plasma. Injection of GK in vivo reduced plasma kininogen levels for over 24 h. GK produced pressor responses only in fish pretreated with the angiotensin-converting enzyme (ACE) inhibitor captopril. This effect was mediated partly through stimulation of alpha-adrenergic receptors. T produced slight pressor responses that were captopril insensitive. These results show that trout possess elements of the KKS system including kallikrein-like enzymatic activity, kininogen, receptor-mediated vascular sensitivity to kallikrein products, and kininolytic activity consistent with ACE (kininase II).
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PMID:Enzymes of the kallikrein-kinin system in rainbow trout. 217 52

Factor XI activity and antigen was purified about 300 fold from human platelets through chromatography on Con-A Sepharose, SP-Sephadex C-50, immobilized goat anti-factor XI, and SP-Sephadex. The partially purified platelet factor XI (Pt-XI) could be activated by activated factor XII generated in situ from single chain factor XI in a reaction requiring high molecular weight kininogen (HMWK) and a surface. Native Pt-XI migrated as a molecule of Mr = 245,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) as identified by Western blotting. On reduction, Pt-XI appeared to have a Mr = 52,000. Neither form was affected by exposure to trypsin. Incubation of Pt-XI with purified factor XII, HMWK, and kaolin produced activated platelet factor XI clotting activity and, concomitantly, the generation over time of a new chain on reduced SDS-PAGE of Mr = 44,500. The coagulant activity of the activated form could be neutralized by diisopropyl flurophosphate (DFP). Incubation of the activated mixture with 3H-DFP followed by reduced SDS-PAGE showed the active site to be associated with a unit of Mr = 44,500. The adsorption domain as defined by adsorption to kaolin was localized to the Mr = 44,500 chain containing the active site. Hence, both active site and adsorption functions, properties of separate chains in plasma factor XI, reside in the same chain of Mr = 44,500 of platelet factor XI.
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PMID:Purification and characterization of platelet factor XI. 227 39


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