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)

The interaction of trypsin with an acid polysaccharide, heparin, at pH 4.2 and 8.0 is studied. Heparin is found to destabilize the enzyme under condition of both autolytic denaturation (pH 8.0) and thermoinactivation (pH 4.2). Data on trypsin inactivation kinetics suggest that the stage of forming molecular complexes with different contents of trypsin and heparin precedes the stage of the enzyme denaturation. Maximal trypsin inactivation rate takes place under equimolar enzyme:heparin ration.
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PMID:[Some peculiarities of trypsin and heparin interaction]. 3 Dec

Large amounts of injected radiolabeled low density lipoproteins have been found by others to accumulate primarily in the liver and studies in various types of isolated cells, including hepatocytes, have indicated the presence of specific cell membrane recognition sites for lipoproteins. In the present studies, the high affinity binding of radiolabeled low density lipoproteins ([125I]LDL, d 1.020--1.063 g/mL) was measured in the major subcellular fractions of porcine liver homogenates. The nuclear and mitochondrial fractions were 1.9- and 1.4-fold enriched in binding activity with respect to unfractionated homogenates and contained 15% and 12% of the total binding activity, respectively. The microsomes, which contained most of the plasma membranes and endoplasmic reticulum, were approximately 4-fold enriched in binding and contained 73% of the binding activity. Microsomal subfractions obtained by differential homogenization and centrifugation procedures were 5.6--7.0-fold enriched in LDL binding and contained 54--58% of the homogenate binding activity. They were separated by discontinuous sucrose density gradient centrifugation into fractions which contained "light" and "heavy" plasma membranes and endoplasmic reticulum. The heavy membrane fraction was 2--4 fold in binding with respect to the parent microsomes (16--22 fold with respect to the homogenate). There was no enrichment of binding activity in the other two fractions. Two plasma membrane "marker" enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, were also followed. Of the two, binding in the sucrose density gradient subfractions most closely followed nucleotide pyrophosphatase, which was also most highly enriched (3.2--3.3-fold) in the heavy membrane fraction, but did not follow it exactly. The enzyme was 2-fold richer in the light membranes than in the parent microsomes, though the light membrane binding activity was only 0.4--1.4 times that of the parent microsomes. High affinity binding was time and temperature dependent, saturable, and inhibited by unlabeled low density lipoproteins but not by unrelated proteins. Binding was stimulated 2--3 fold Ca2+, was not affected by treatment with Pronase or trypsin and was inhibited by low concentrations of phospholipids and high density lipoproteins (HDL). Heparin-Mn2+ treatment of HDL did not affect its ability to inhibit [125I] LDL binding. The LDL recognition site was distinct from the liver membrane asialoglycoprotein receptor; LDL binding was not inhibited by desialidated fetuin. We conclude that porcine liver contains a high affinity binding site that recognizes features common to both pig low density and high density lipoproteins. Further studies may elucidate the significance of this binding site in lipoprotein metabolism.
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PMID:Isolation of a porcine liver plasma membrane fraction that binds low density lipoproteins. 8 56

1. The addition of heparin to the culture fluid of mouse tibiae or calvaria did not cause any significant resorption of bone collagen or mineral. However, heparin (or analogue sulfated polyanions), enhanced greatly the amount of latent, trypsin-activatable collagenase (i.e. procollagenase) released by the bones in the medium without influencing that of directly active collagenase which was always very low. Heparin appeared to act by increasing the production of the enzyme which is immediately excreted. Procollagenase and collagenase are not stored in bone tissue, even under conditions where it is in active resorption. 2. Parathyroid hormone induced in the explants a resorption of both mineral and collagen that was inhibited by calcitonin. These hormones, however, had no influence on the release of procollagenase or collagenase either in the presence or in the absence of heparin. 3. Once activated, bone collagenase digested the collagen of the bone explants, and more extensively after their demineralization. Thus the latent collagenase that accumulates around non-resorbing bones has to be considered as a precursor, (and not as a residue), of active enzyme. 4. Active collagenase added to incipient cultures of bones disappeared with a half-life of 24 h. The lost enzyme could, however, not be reactivated by trypsin and thus was not transformed into latent procollagenase.
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PMID:Collagenase, procollagenase and bone resorption. Effects of heparin, parathyroid hormone and calcitonin. 22 39

The effect of heparin on the activation of trypsinogen by enterokinase and on trypsin activity has been investigated. Proteolytic activity of trypsin has been determined using caseinolytic method. It has been found that heparin inhibits trypsinogen activation only when it is preincubated with proenzyme before introduction of enterokinase to the tested system. In these experimental conditions heparin in final concentrations from 1 to 20 U/ml exhibits inhibitory effect diminishing trypsinogen activation to about 65% initial activity and in higher concentrations only to 50%. Heparin introduced to the tested system simultaneously with enterokinase or to the active trypsin did not appear evident inhibitory effect.
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PMID:The inhibitory effect of heparin on trypsinogen activation with enterokinase. 93 May 38

A fusion protein of acidic fibroblast growth factor and diphtheria toxin A-fragment was disulfide-linked to the toxin B-fragment. The complex bound specifically to diphtheria toxin receptors, and subsequent exposure to low pH induced the fusion protein to translocate to the cytosol. Heparin, inositol hexaphosphate and inorganic sulfate strongly increased the trypsin resistance of the growth factor part of the fusion protein, indicating tight folding, and they prevented translocation of the fusion protein to the cytosol. The data indicate that only a more disordered form of the growth factor is translocation competent.
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PMID:Tight folding of acidic fibroblast growth factor prevents its translocation to the cytosol with diphtheria toxin as vector. 128 50

Conditioned medium from Sertoli cells, prepared from testes of 20-day-old rats, contains component(s) that inhibit the incorporation of [3H]-thymidine into DNA of peritubular myoid cells (PMC) and inhibit the proliferation of PMC. These components are trypsin-resistant, heat-stable compounds having a molecular weight less than 30,000. The active inhibitory components in Sertoli cell conditioned medium are inactivated by treatment with heparinase, but not by treatment with hyaluronidase or chondroitin sulfate lyases. Addition of heparin or heparan sulfate results in inhibition of DNA synthesis by PMC in a dose-dependent manner, whereas other glycosaminoglycans (GAGs) examined (hyaluronic acid, keratan sulfate, and chondroitin sulfate) have no detectable effects. Heparin and heparan sulfate are unique among GAGs tested in inhibiting the characteristic multilayer growth pattern of PMC following the attainment of confluence in serum-rich medium. On the basis of these and other data presented, it is concluded that heparin and other heparin-like GAGs synthesized by Sertoli cells are implicated in the modulation of growth of PMC in vitro during co-culture. It is postulated that heparin may play a similar role in maintaining the quiescent peritubular myoid cell phenotype in vivo.
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PMID:Sertoli cells in culture secrete paracrine factor(s) that inhibit peritubular myoid cell proliferation: identification of heparinoids as likely candidates. 171 60

Although heparin was reported in the 1960s to inhibit renin activity, this has not always been confirmed by other investigators. Hence, we re-examined whether heparin really inhibits renin or not. Renin activities were determined by radioimmunoassay of angiotensin I generated at pH 7.4. (i) No significant difference was found between the two kinds of plasma samples obtained with heparin and with EDTA as anticoagulant, in ARC (renin activity with addition of sheep renin substrate), TRC (ARC after activation of inactive renin by trypsin), or PRA (plasma renin activity without additional substrate). (ii) Even in higher concentrations of heparin up to 500 U/mL, neither PRA, ARC, nor TRC of plasma was affected significantly. (iii) Heparin, in concentrations up to 500 U/mL, exerted no significant effect on TRC of the media of human vascular smooth muscle cell culture. In conclusion, heparin does not exert any significant inhibitory effect on human renin nor does it affect activation of inactive renin by trypsin in the range of concentration of practical use, under the conditions employed in this study.
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PMID:Does heparin inhibit renin activity? 175 38

Mesangial cells in culture develop hillocks, which are composed of aggregates of cells, necrotic cellular debris, and extracellular matrix material. The significance and mechanism of their formation are unknown. To determine whether a proliferative component is involved in hillock formation, cells were treated with heparin or irradiated to inhibit proliferation. Heparin caused a 50% inhibition of mesangial cell growth and stimulated hillock formation three-fold to fourfold. Irradiated cells developed hillocks to the same extent as did nonirradiated cells, and the addition of heparin also increased hillock formation threefold to fourfold. Dextran sulfate and chondroitin B sulfate had no effect on mesangial cell hillock formation. Mesangial cells cultured in the presence of 50 micrograms/mL of heparin were less tightly adhered than nontreated cells, as assessed by a trypsin adhesion assay (control cells, 12% detached; heparin-treated cells, 72% detached). Thus, it appears that heparin, a glycosaminoglycan with potent antimitogenic activity, stimulates mesangial cell hillock formation, possibly by decreasing cell adhesion.
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PMID:Heparin increases hillock formation in mesangial cell cultures. 177 96

Chymotrypsin-like activity of multicatalytic proteinase (MCP) purified from human erythrocytes was selectively activated 2.5--3.5-fold by sulfated glycolipids such as galactosylceramide sulfate (SM4) and lactosylceramide sulfate (SM3) but not by other glycolipids including galactosylceramide (GalCer), lactosylceramide (LacCer), GD1a, GM1 and GM3. Heparin also selectively activated trypsin-like activity 2.5-fold, while other mucopolysaccharides did not. This proteinase molecule bound specifically and with high affinity to both SM4 and SM3, but not to GalCer, LacCer and GM3. The binding of SM4 and SM3 to the enzyme molecule was also confirmed by thin layer chromatography.
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PMID:Human erythrocyte multicatalytic proteinase: activation and binding to sulfated galacto- and lactosylceramides. 182 64

Heparin depresses the second-order rate constant ka for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. High molecular mass heparin decreases ka from 1.3 x 10(7) M-1 s-1 to a limit of 4.6 x 10(4) M-1 s-1. Low molecular mass heparin is about 7-fold less effective. Dermatan sulfate and chondroitin sulfate are less efficient. Heparin preparations used in clinical care also strongly depress ka when tested at concentrations corresponding to their clinical efficacy. Heparin also decreases the ka for the elastase/eglin c and the cathepsin G/alpha 1-proteinase inhibitor systems but not that for the alpha 1-proteinase inhibitor/pancreatic elastase or trypsin pairs. These results, together with Sepharose-heparin binding studies, indicate that the ka-depressing effect of the polymer is related to its ability to form a tight complex with elastase but not with alpha 1-proteinase inhibitor. One mol of high molecular mass heparin binds 3 mol of neutrophil elastase with a Kd of 3.3 nM. Low molecular mass heparin binds elastase with a 1:1 stoichiometry and a Kd of 89 nM. For both heparins ka is lowest when elastase is fully saturated with heparin. From this we conclude that heparin decreases ka, because the heparin-elastase complex is able to slowly react with alpha 1-proteinase inhibitor and not because the inhibitor slowly dissociates the heparin-elastase complex. These findings may have important pathophysiological bearing.
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PMID:Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. 186 57


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