Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Salt extracts of the extracellular matrix (ECM) that is produced by vascular and capillary endothelial cells contain mitogens that are indistinguishable from basic and acidic fibroblast growth factors (FGFs). The biological activity found in these extracts is retained by heparin-Sepharose affinity columns and elutes with salt concentrations similar to those required to elute FGFs (i.e. 1.1 - 2M NaCl). Antisera raised against synthetic fragments of basic and acidic FGF crossreact with the ECM-derived mitogens. Radioiodinated basic FGF binds to the ECM formed by both vascular and capillary endothelial cells, a result that is consistent with the observation that FGF-like mitogens are found on the ECM. The binding of FGF to the ECM is negligible when the ECM has been pretreated with heparinase or heparitinase suggesting that the mitogen is interacting with a heparin-like glycosaminoglycan in the ECM. The digestion of the ECM with several grades of hyaluronidase, chondroitinase or chondro-4-sulfatase or chondro-6-sulfatase has little or no effect on 125I-FGF binding to the ECM. In view of the fact that many, if not all cells, produce heparan sulfates and that these glycosaminoglycans are associated with the external surface of the cell and the ECM, a model is proposed suggesting that the neovascular response induced by tumours and some normal tissues may be mediated at least in part, by the initial release of heparinase-like enzymes rather than angiogenic factors (FGFs) per se. The release of these enzymes would effectively mobilize a secondary local release of FGF from the ECM which then induces a proliferative response.
 ...
PMID:Fibroblast growth factors are present in the extracellular matrix produced by endothelial cells in vitro: implications for a role of heparinase-like enzymes in the neovascular response. 243 94

The development of a safe and efficient bioreactor design has remained a challenge for the clinical application of immobilized enzymes. Specifically, the use of immobilized heparinase I has been the target of many studies to make heparin anticoagulation therapy safer for the critically ill patient with kidney failure or heart disease. We have investigated the use of Taylor-Couette flow for a novel type of bioreactor. In a previous study, we showed that the fluidization of agarose immobilized heparinase within Taylor vortices in whole blood can lead to extensive blood damage in the form of cell depletion and hemolysis. Based on these findings, we designed and developed a reactor, referred to as vortex-flow plasmapheretic reactor (VFPR), that incorporated plasmapheresis and fluidization of the agarose in the reactive compartment, separate from the whole-blood path. In the present study, immobilized heparinase I was tested as a means of achieving regional heparinization of a closed circuit. This is a method in which heparin is infused into the extracorporeal circuit predialyzer and neutralized postdialyzer. Saline studies were performed with an immobilized heparinase I-packed bed and with the VFPR. An in vitro feasibility study was performed with the VFPR using human blood. The VFPR achieved heparin conversions of 44 +/- 0.5% and 34 +/- 2% in saline and blood, respectively. In addition, the VFPR caused no blood damage. We report a novel method to achieve fluidization which depended on secondary, circumferencial flow, and was independent of the primary flow through the device.
 ...
PMID:Regional heparinization via simultaneous separation and reaction in a novel Taylor-Couette flow device. 1039 18

Salt-active acharan sulfate lyase (no EC number) has been purified from Bacteroides stercoris HJ-15, which was isolated from human intestinal bacteria with GAG degrading enzymes. The enzyme was purified to apparent homogeneity by a combination of QAE-cellulose, diethylaminoethyl (DEAE)-cellulose, CM-Sephadex C-50, HA ultrogel and phosphocellulose column chromatography with the final specific activity of 81.33 micro mol x min-1 x mg-1. The purified salt-active acharan sulfate lyase was activated to 5.3-fold by salts (KCl and NaCl). The molecular weight of salt-active acharan sulfate lyase was 94 kDa by SDS/PAGE and gel filtration. The salt-active acharan sulfate lyase showed optimal activity at pH 7.2 and 40 degrees C. Salt-active acharan sulfate lyase activity was potently inhibited by Cu2+, Ni2+ and Zn2+. This enzyme was inhibited by some agents, butanediol and p-chloromercuric sulfonic acid, which modify arginine and cysteine residues. The purified Bacteroidal salt-active acharan sulfate lyase acted to the greatest extent on acharan sulfate, to a lesser extent on heparan sulfate and heparin. The biochemical properties of the purified salt-active acharan sulfate lyase are different from those of the previously purified heparin lyases. However, these findings suggest that the purified salt-active acharan sulfate lyase may belong to heparin lyase II.
 ...
PMID:Purification and characterization of novel salt-active acharan sulfate lyase from Bacteroides stercoris HJ-15. 1286 91