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)

A method of preparation of papain (EC 3.4.22.2) from relatively soluble types of latex of Carica papaya, including spray-dried latex produced by a controlled and relatively mild process, was devised. Spray-dried latex dissolves easily in water up to 350mg/ml at 22 degrees C, which corresponds to approx. 230mg of protein/ml. When the usual method of preparation of crystalline papain contaminated only by its oxidation products, developed by Kimmel & Smith [J. Biol. Chem. (1954) 207, 515-531], is applied to spray-dried latex, the result is a preparation of papain heavily contaminated by chymopapains A and B (EC 3.4.22.6), and to a lesser extent by papaya peptidase A. This applies also to other types of papaya-latex currently commercially available, which, though less soluble than spray-dried latex, are more soluble than the types of latex available when the method of Kimmel & Smith (1954) was developed. This contamination is avoided by adjusting the concentration of the initial latex extract to 65mg of protein/ml (or less) before salt fractionation. For spray-dried latex this corresponds to 100mg of latex/ml. Papain isolated from spray-dried latex was characterized by using 2,2'-dipyridyl disulphide and 4-chloro-7-nitrobenzofurazan as thiol-specific reactivity probes and alpha-N-benzoyl-l-arginine ethyl ester as substrate. Papain isolated from this source appears to have the same catalytic-centre characteristics as papain isolated previously from latex produced by harsher methods. The catalysis of the hydrolysis of alpha-N-benzoyl-l-arginine ethyl ester by the mixture of thiol proteinases extracted from spray-dried latex by application of the method of Kimmel & Smith (1954) appears to obey Michaelis-Menten kinetics. The presence of the other enzymes results in an increase in the value of K(m) and a decrease in the catalytic-centre activity (k(cat.)) relative to the values for the catalysis by papain.
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PMID:A necessary modification to the preparation of papain from any high-quality latex of Carica papaya and evidence for the structural integrity of the enzyme produced by traditional methods. 43 50

Two proteases, one of which is papaya peptidase A and the other a previously unknown enzyme in papaya latex have been purified to homogeneity in a simple two stage process. Both are markedly less reactive than papain or chymopapain. Each has a molecular weight of 24,000, N-terminal sequences commencing Leu-Pro-Glu, and contains no carbohydrate. Their amino acid compositions differ for several residues. The essential -SH groups of the enzymes examined appear to be 'masked' in the native state.
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PMID:A purification and some properties of two proteases from papaya latex. 47 25

Sequences to residue 17 have been determined for the three Papaya cysteinyl proteases, chymopapain and papaya peptidase A and B. Extensive homologies were found for these three enzymes and with papain and bromelain. These results suggest that the five sulphydryl enzymes discussed derive from a common ancestral gene.
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PMID:N-Terminal homology in three cysteinyl proteases from Papaya latex. 51 21

To attempt to understand the etiology of failures of chemonucleolysis, biochemical analyses were performed on intervertebral disk material to determine if the enzyme had actually digested the nucleus pulposus proteoglycans. This information was then correlated with the clinical laboratory data to see if a pattern evolved for the failures. Nine chymopapain treated disks, 6 untreated herniated disks and 6 lumbar disks from scoliotic patients were obtained at surgery. The results indicated that 6 out of 9 patients treated with chymopapain had a marked reduction in the proteoglycan (hexosamine) content of their disk compared to the untreated controls. There was a significant inverse correlation of intrinsic lysosomal enzymes and hexosamine content in those cases where the chymopapain failed to destroy the proteoglycan. The other 3 patients, however, had hexosamine levels virtually identical to those disks not treated with chymopapain. The clinical evaluation, consisting of preoperative myelograms, diskograms, the surgeon's observations at laminectomy and evaluation of the postoperative regimen did not explain the failures. This study suggests that the chymopapain failures are not the result of inactivity of the enzyme or failure to digest the nuclear material in at least 6 of the 9 cases. However, there were 3 patients where either the enzyme was not reaching the nuclear material or it was inactive.
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PMID:Combined biochemical and clinical investigation of chemonucleolysis failures. 59 99

Lateral X-rays of lumbosacral spines of 76 patients who received chymopapain injection for lumbar disk lesions after a positive myelogram and diskogram were examined and measured to determine the degree of narrowing which occurred after injection of the enzyme. There were 2 groups of patients, those with clinically good results after injection, and those with poor results. Measurements were made of the injected and adjacent noninjected disk spaces. The validity of the method used with established by a correlation of 0.95 over a period of time for the uninjected disks. The narrowing after injection was significant at the p less than 0.01 level for both clinical successes and failures, but the degree of narrowing was significantly greater for the clinically good results.
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PMID:An evaluation of narrowing following intradiskal injection of chymopapain. 60 73

In 13,700 patients who received one or more lumbar disc injections of chymopapain, 401 complications, adverse reactions, and delayed untoward events were recorded, including eight deaths. The deaths were secondary to anaphylaxis, pulmonary embolism, discitis with subacute bacterial endocarditis, ruptured abdominal aortic aneurysms (two patients), encephalitis (of unknown etiology), and myocardial infarction. Of these, the deaths secondary to anaphylaxis and discitis with subacute bacterial endocarditis can be attributed directly to the procedure of chemonucleolysis.
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PMID:Complications of chemonucleolysis for lumbar disc disease. 61 47

A solid phase radioimmunoassay, similar to the RAST, was developed in an attempt to predict anaphylactic reactions in patients injected with the proteolytic enzyme chymopapain, used in therapy for prolapsed intervertebral disc. The test measured the serum content of anti-chymopapain antibodies of the IgE class. Of 1263 patients tested, twelve gave anaphylactic reactions. The test was predictive for seven of them (58%), while sixty were false positives. Measurements were also made of anti-chymopapain IgE or other classes of antibodies which developed in the sera of patients after chymopapain injection. The presence of antibodies to chymopapain in individuals who had not been injected was also demonstrated.
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PMID:Correlation between hypersensitivity to parenteral chymopapain and the presence of IgE anti-chymopapain antibody. 70 10

Three hundred and nine patients having herniated nucleus pulposus syndrome were treated by chemonucleolysis with chymopapain. We analyzed the results of that treatment in the first 100 patients who had been followed up for two years. No significant allergic reactions, deaths, spinal cord injury or paralysis occurred. One patient had pulmonary embolus and another had a disk space infection. Diskitis did not occur. Of the 100 patients receiving chymopapain, 71% of the results were rated good to excellent; of those in a comparably followed-up group of 100 patients who underwent surgery, 63% of the results were rated good to excellent. The end result was achieved more quickly after chemonucleolysis and with less physiologic stress on the patient. The beneficial result was considered to be long lasting, and in our opinion, the quality of the end result was superior after chemonucleolysis.
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PMID:Chemonucleolysis vs laminectomy. 72 23

The results of chemonucleolysis in 48 patients with lumbar disc disease revealed marked improvement in 58%, slight improvement in 23%, and no improvement in 19%. Serious anaphylactic reactions occurred in two patients. These results and those of other neurosurgical and orthopaedic studies are summarized and compared with the 70% improvement rate obtained with a placebo in a recent double blind controlled cooperative study. Only those few investigators participating in the double blind study are now permitted to use intradiscal chymopapain. It is concluded that the ultimate place of chemonucleolysis, if any, in the treatment of ruptured lumbar discs remains to be determined.
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PMID:Chymopapain in the treatment of ruptured lumbar discs. Preliminary experience in 48 patients. 77 45

The authors report 66 patients with signs, symptoms, and a myelographic abnormality of herniated lumbar disc, who were not responsive to conservative treatment. The discs were injected at random with either chymopapain or a placebo. Neither patient nor surgeon knew which agent was used until after the results had been tabulated. Unless early laminectomy was necessary for intractable pain, all patients were followed for 2 months or more. There was no statistically significant difference in incidence or quality of improvement between the two groups: chymopapain was successful in 58% while placebo was successful in 49% (p = 0.15). Early results from this study indicate that most, if not all, of the putative effectiveness of chemonucleolysis probably derives from a placebo effect.
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PMID:Double-blind evaluation of intradiscal chymopapain for herniated lumbar discs. Early results. 78 27


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