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:3.4.22.6 (chymopapain)
407 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chymopapain degrades the nucleus pulposus portion of the intervertebral disk of rabbits. The degradation is not grossly visible until 15 days post-injection. Depolymerization of the chondromucoprotein and decreases in the ability of a disk to imbibe fluid, is, in effect, a "chemical decompression" of the nucleur pulposus. The enzyme must come into direct contact with the chondromucoprotein complex of the disk material, and to a significant extent also must reach the area of disk material adjacent to the herniated annulus. Rapid depolymerization of the chondromucoprotein complex on a biomechanical level, and "decompression" of disk material on a biomechanical level can be correlated with relief of pain in all types of disk herniation in human beings. A primary biochemical change in the disk material would lead to a secondary decrease in inflammation if the change led to a "decompression" of the chondromucoprotein. Since the primary effect of chymopapain is on the chondromucoprotein of the disk, beneficial results would not be expected if nerve root compression is due to bony impingement or scar tissue following previous surgery. Chymopapain did not seem to possess any anti-inflammatory properties when bone was used as an irritant under a nerve root. However, this was technically difficult to evaluate and the possibility that chymopapain may also interfere with a chemical mediator of pain or interfere directly with an inflammatory reaction secondary to root compression can not be excluded.
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PMID:Experimental studies on the effect of chymopapain on nerve root compression caused by intervertebral disk material. 112 86

Studies were carried out to demonstrate residual chymopapain activity in intervertebral discs after chemonucleolysis; protease assay, enzyme-linked immunosorbent assay, and immunohistochemical localization of the chymopapain in the disc tissue were done. Chymopapain, one milligram per level, was injected into the normal lumbar intervertebral discs of adult mongrel dogs and the discs were excised after two weeks. Proteolytically active chymopapain was still present in the extract of intervertebral disc at this time. The proteolytic activity was decreased by sulfhydryl inhibitors but not by inhibitors of metalloproteases or serine proteases. Protease and enzyme-linked immunosorbent assays showed that 0.60 +/- 0.48 per cent and 0.49 +/- 0.38 per cent of the original dose was present two weeks after the injection. Chymopapain was shown by immunohistochemical staining to be diffusely located throughout the extracellular matrix of the anulus fibrosus and the nucleus pulposus. Some cells, located mainly in the inner portion of the anulus, contained vacuoles filled with immunoreactive product.
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PMID:Residual chymopapain activity after chemonucleolysis in normal intervertebral discs in dogs. 831 35

Complete yet nontoxic removal of tumor cells from autologous marrow grafts has proved difficult. New methods for separating normal stem cells from tumor cells are needed. The CD34+ cells in bone marrow, 1-2% of the low-density leukocytes, include precursors of all lymphohematopoietic lineages and probably also the primitive cells responsible for engraftment. A nontoxic, inexpensive, reproducible, and clinically applicable method for positive selection of CD34+ cells was developed. Paramagnetic microspheres coated with goat anti-mouse IgG1 are used to partition the cells; brief incubation with chymopapain is used to release them from the beads. Chymopapain exposure does not injury colony-forming cells or delay engraftment in rodents. Clinical volumes of bone marrow can be processed rapidly. In pilot experiments, the resulting grafts have a purity of 85-99% CD34+ cells and 40% median recovery of the assayable colony-forming cells. These studies form the background for a Phase I trial of autologous BMT using CD34+ stem cells.
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PMID:Selection of normal human hematopoietic stem cells for bone marrow transplantation using immunomagnetic microspheres and CD34 antibody. 171 50

The present study on chemonucleolysis was conducted to determine the influence of chymopapain dose level and patient age on the degree and mode of the response and regeneration of the intervertebral disc. Chymopapain at various doses was injected into the intervertebral discs of young (8-week-old) and mature (20-week-old) rabbits respectively for a histological study. In rabbits undergoing high dose injection, not only the nucleus pulposus but also the inner layer of the annulus fibrosus was digested. Regeneration hardly occurred, and only a slight amount of scar tissue appeared in many animals. At lower dose, the annulus fibrosus remained intact and the posterior inner layer of the annulus fibrosus mainly proliferated toward the anterior portion of the disc, filled the space of digested nucleus pulposus, and restored disc height. This regeneration process was not thought to be specific to the damages caused by chymopapain but rather a common response of injured intervertebral discs.
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PMID:[Histological study on chemonucleolysis with special reference to the relationship between the dose of chymopapain and disc regeneration]. 205 37

Chymopapain (EC 3.4.22.6) was purified from commercially available dried latex of papaya (Carica papaya) by extraction at acidic pH, cation-exchange chromatography and active site-directed affinity chromatography on immobilized alanyl-phenyl-alaninaldehyde semicarbazone, with elution by mercuric chloride. The product was found by immunoassay to be essentially free of the other cysteine proteinases from papaya, including papaya proteinase IV, and was fully active. The rate of alkylation of the active site cysteine of chymopapain by iodoacetate was found to be sufficiently rapid and selective for this reagent to be used as an active-site titrant.
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PMID:The preparation of fully active chymopapain free of contaminating proteinases. 208 14

Chymopapain is a polypeptide of 218 amino acid residues. It has considerable structural similarity with papain and papaya proteinase omega, including conservation of the catalytic site and of the disulphide bonding. Chymopapain is like papaya proteinase omega in carrying four extra residues between papain positions 168 and 169, but differs from both papaya proteinases in the composition of its S2 subsite, as well as in having a second thiol group, Cys-117. Some evidence for the amino acid sequence of chymopapain has been deposited as Supplementary Publication SUP 50153 (12 pages) at the British Library Document Supply Centre, Boston Spa., Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms indicated in Biochem. J. (1990) 265, 5. The information comprises Supplement Tables 1-4, which contain, in order, amino acid compositions of peptides from tryptic, peptic, CNBr and mild acid cleavages, Supplement Fig. 1, showing re-fractionation of selected peaks from Fig. 2 of the main paper. Supplement Fig. 2, showing cation-exchange chromatography of the earliest-eluted peak of Fig. 3 of the main paper, Supplement Fig. 3, showing reverse-phase h.p.l.c. of the later-eluted peak from Fig. 3 of the main paper, and Supplement Fig. 4, showing the separation of peptides after mild acid hydrolysis of CNBr-cleavage fragment CB3.
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PMID:The amino acid sequence of chymopapain from Carica papaya. 210 78

Because arachnoiditis occurred in a previous experimental study, the authors performed additional experimental injections of chymopapain in the epidural space. Four monkeys received epidural injections of 100 units of chymopapain in 1.2 mL of saline on days 1, 8, and 16 of the experiment; four control animals received injections of 1.2 mL of 0.9% saline on the same days. Both groups were killed on the 84th day. The dural sac was removed, fixed, sectioned, stained, and examined microscopically. No significant changes were found in the arachnoid, dura, or epidural space of the treated animals. Chymopapain, even if injected repeatedly into the epidural space, does not cause significant scarring in the meninges.
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PMID:Effect of repeated injections of chymopapain in the epidural space. 229 52

Immediate and long-term microvascular effects of chondroitinase ABC, 200 unit/ml, were analyzed in ten hamsters. The immediate effects on the microcirculation were studied by vital microscopy following local injection in the cheek pouch. There were no detectable effects on the microvascular blood flow during the 60 minutes of observation for chondroitinase ABC or the control. A therapeutic concentration (2000 pKat/ml) of chymopapain stopped the microcirculation in the injected area immediately, with numerous microbleedings at the border zone. Long-term effects were studied after subcutaneous injections in the ears of six rabbits. Chondroitinase ABC and the control did not cause any macroscopic or microangiographic effects. However, light microscopy showed a moderate inflammatory reaction in the subcutaneous layer for both chondroitinase ABC and the control. Chymopapain induced severe effects on the cartilage and surrounding tissues. Microangiography revealed a vessel-free zone at the injection site. Since 200 units/ml of chondroitinase ABC is four to eight times higher than the concentration that might be used for chemonucleolysis, i.e., dissolution of intervertebral discs by local enzyme injection, the present investigation suggests a wide margin of safety regarding the potential effects on blood vessels in tissues surrounding the disc.
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PMID:Microvascular effects of chondroitinase ABC and chymopapain. An in vivo experimental study on hamsters and rabbits. 237 64

An experimental model of disc herniation in tail discs of rats is described. Constant result on nucleus hernia and intervertebral narrowing were obtained by an easy manipulation on numerous rats. Intradiscal injection of aprotinin produced a widening of the disc height. Trypsin, collagenase, chymopapain, and hyaluronidase induced a narrowing of disc height; trypsin induced macroscopic necrosis of the soft surrounding tissues; and collagenase had a destructive effect on nucleus pulposus, annulus fibrosus, and even on end-plates. Chymopapain and hyaluronidase acted mainly on nucleus pulposus. Hyaluronidase could be of interest as a nucleolytic drug and needs further studies on optimal dosage and lack of side effects in the surrounding tissues before injecting it into human discs.
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PMID:Experimental model of disc herniations in rats for study of nucleolytic drugs. 244 86

The amino-acid sequence of chymopapain is presented. It was isolated from the latex of the fruits from the tropical species Carica papaya L. and is, besides papain and papaya proteinase omega, the third thiol proteinase from this source. The primary structure contains 218 amino-acid residues. It was deduced from sequence analysis of the native enzyme and of peptides obtained by tryptic, chymotryptic, peptic, thermolysinolytic and mild acidic hydrolysis. Out of a total of eight cysteine residues, six are involved in the formation of three disulfide bonds, the location of which has been established with the help of peptic and thermolysinolytic peptides and fragments, obtained by mild acidic hydrolysis. Chymopapain shares 126 identical amino-acid residues (58%) with papain and 141 (65%) with papaya proteinase omega, including the three disulfide bridges and the free cysteine in position 25, required for activity. Except some amino-acid residues in the substrate-binding site, all residues involved in the catalytic mechanism are conserved. The homology between papaya proteinases is discussed.
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PMID:The thiol proteinases from the latex of Carica papaya L. III. The primary structure of chymopapain. 250 Sep 50


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