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)

Acidic proteins tend to be degraded more rapidly than neutral or basic proteins in rat liver, skeletal muscle, kidney and brain and in mouse liver and skeletal muscle. We now report a similar relationship among soluble proteins from rat lung, heart and testes, and from human fibroblasts and mouse-embryo cells grown in culture. These findings indicate that the correlation between protein net charge and degradative rate is a general characteristic of intracellular protein degradation in mammals. This relationship between isoelectric point and half-life appears to be distinct from the previously reported correlation between subunit molecular weight and protein half-lives. The more rapid degradation of acidic proteins does not result from their being of larger molecular weight than neutral or basic proteins. Furthermore, proteins within specific isoelectric point ranges still exhibit a relationship between subunit size and half-life. Finally, a group of membrane or organelle-associated proteins that are insoluble in phosphate-buffered saline and water but soluble in 1% Triton X-100 exhibit a correlation between size and half-life, but not between net charge and half-life. The biochemical reasons for the relationship between protein isoelectric point and half-life are unclear, although several possible explanations are presented. It is not due to a greater sensitivity of acidic proteins to proteolytic attack since experiments with a variety of endoproteinases, including trypsin, chymotrypsin, Pronase, papain, chymopapain, Staphylococcus aureus V8 proteinase, pepsin and lysosomal cathepsins from rat liver, have failed to demonstrate more rapid digestion of acidic proteins.
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PMID:Studies on the relationship between the degradative rates of proteins in vivo and their isoelectric points. 3 75

Experience with chymopapain chemonucleolysis in 1,200 cases of lumbar disk disease indicates that it is an effective method of relieving pain resulting from an abnormal intervertebral disk. Complications were few; anaphylaxis occurring immediately after injection was by far the most serious. With the use of a corticosteroid and an antihistamine in preoperative preparation, the incidence of anaphylaxis had dropped, although it still occurs. On long-term follow-up, chemonucleolysis appears to be as good as laminectomy in properly selected cases.
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PMID:Chymopapain chemonucleolysis in lumbar disk disease. 12 15

In the first of a two-part study, the authors review the known biochemical, pharmacological, toxicological, and experimental data concerning chymopapain and the intervertebral disc. They describe the action of this proteolytic enzyme, which apparently disrupts the protein mucopolysaccharide component of disc material, most marked in the nucleus pulposus. A rapid conversion to collagen causes a loss of disc space height; toxicity appears to result from alteration of bonding between capillary endothelial cells that in turn produces hemorrhage. Part 2 reviews significant reported results and complications of clinical chemonucleolysis.
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PMID:Chymopapain treatment of intervertebral disc disease. 12 75

Pre-injection psychological test scores, surgeon ratings, and patient biographical data were evaluated as predictors of success of chymopapain injection therapy in 130 patients who would otherwise have been treated by laminectomy. Three psychological tests were administered to each patient: the Minnesota Multiphasic Personality Inventory, the Cornell Medical Index, and the Quick Test (a measure of mental ability). In addition, the surgeons rated their patients on a five-point scale immediately after injection relative to their suitability for injection therapy and at one year relative to the objective and symptomatic results. The MMPI hysteria and hypochondriasis scales and the surgeon's rating of the psychogenic component of the patient's pain were predictive of the result of chemonucleolysis. The patient's biographical data which consisted of age, sex, marital status, occupation, and education were not related to postoperative outcome.
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PMID:Preoperative psychological tests as predictors of success of chemonucleolysis in the treatment of the low-back syndrome. 12 36

Chemonucleolysis is a procedure for treatment of low back pain due to discogenic disease in which the drug chymopapain is injected into lumbar disks to produce chemical dissolution of the nucleus pulposus. More than 15,000 cases have been treated by chemonucleolysis world-wide. Anaphylaxis after the injection of chymopapain occurs in about 1% of such cases. The two cases described in this paper are the only known deaths due to anaphylaxis. Both patients suddenly became hypotensive after injection of chymopapain into a disk. One patient died shortly after this, whereas the second patient died of the complications of prolonged shock.
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PMID:Two anaphylactic deaths after chemonucleolysis. 12 1

With the apparent indefinite postponement of the release of chymopapain for lumbar disk disorders, it seems appropriate to review critically the proliferation of proposed methods of management of this common complaint, particularly the numerous exercise regimens which have been set forth as helpful. A critical review of these regimens quickly reveals that the majority are propounded with considerably more confidence than statistical proof of their efficacy. The following is a delineation of the results of a critical review of the literature, with emphasis on those few studies which have been statistically validated. The physician has an obligation to attempt conservative management of discogenic disease with methods of demonstrated efficacy before recommending invasive procedures such as laminectomy or chemonucleolysis.
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PMID:Conservative management of low back pain. 13 Jun 80

A prospective study of 480 patients who underwent enzymatic dissolution of the nucleus pulposus with chymopapain is reported. Seventy per cent of patients with the clincial criteria for a disc herniation had a favourable response to chemonucleolysis. The commonest cause of failure was persistent back pain. In patients with sequestered discs or lateral recess stenosis surgical intervention was not made more difficult by chemonucleolysis. Those with a previous operation, spinal stenosis or psychogenic components to the disability had very poor results. Complications were few and easily managed.
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PMID:Chemonucleolysis. 13 12

Chromatography on a column of SP-Sephadex shows that commercial chymopapain contains three components with proteolytic activity. Each behaves as a single protein upon rechromatography and electrophoresis on polyacrylamide gels. The major component, which represents 31% of the activity applied to the column and is the most basic protein, was identified as papaya peptidase A. This enzyme has no methionine and isoleucine on its N-terminus. Its molecular weight is about 24,000 as determined by sodium dodecyl sulfate polyacrylamide electrophoresis and sedimentation equilibrium centrifugation. Its fluorescence emission as a function of pH resembles that for unactivated papain. Reduction is required for full activity, and in general it is less active than papain against substrates such as casein, N-benzoyl-L-arginine ethyl ester, N-tosyl-L-arginine methyl ester, N-benzoyl-L-arginineamide, and N-benzoyl-DL-arginine p-nitroanilide. Of the other components isolated from crude chymopapain, the more acidic enzyme contains 20% of the activity applied to the column, has a molecular weight of about 25,000, and N-terminal residues of tyrosine and glutamic acid. The other enzyme represents 26% of the initial activity, has a molecular weight of about 28,000 and tyrosine on its N-terminus. Both proteins have a single residue of methionine per molecule. The more acidic component resembles chymopapain A, and the other enzyme is similar to chymopapain B.
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PMID:Isolation and characterization of papaya peptidase A from commercial chymopapain. 24 Mar 90

Sixty-six patients with symptomatic herniated lumbar discs refractory to the usual conservative management were allocated at random into one of two treatment groups according to a double-blind protocol: 31 received chymopapain intradiscally (chemonucleolysis) and 35 received a placebo intradiscally. Symptoms remained significantly improved 1 year or more after injection for 55% of those treated with chymopapain and for 46% of those treated with placebo. The difference is not statistically significant. However, to discard chemonucleolysis on the basis of this one small clinical trial may be premature. Since continuing controversy has re-established a climate in which another double-blind study of chemonucleolysis is ethically feasible and scientifically desirable, we favor additional clinical trials under a tightly controlled protocol to help resolve the issue.
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PMID:Double-blind evaluation of chemonucleolysis for herniated lumbar discs. Late results. 36 87

In three cases in which chemonucleolysis with chymopapain was used for the treatment of back and sciatic pain, gas from the vacuum phenomenon of a degenerated lumbar intervertebral disc was recovered. In one of these, the gas analyzed by gas chromatography contained 90%--92% nitrogen.
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PMID:Analysis of gas in vacuum lumbar disc. 41 44


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