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)

In November 1982, the Federal Drug Administration approved Chymodiactin, chymopapain in injection form, for the treatment of herniated intervertebral discs. This procedure, termed chemonucleolysis, requires radiologic support. This article describes the anatomy, pathology, and special techniques related to chemonucleolysis and defines the role of the radiologic technologist in the completion of this procedure.
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PMID:Chemonucleolysis. 334 Jul 46

Chymopapain A was isolated from the dried latex of papaya (Carica papaya) by ion-exchange chromatography followed by covalent chromatography by thiol-disulphide interchange. The latter procedure was used to produce fully active enzyme containing one essential thiol group per molecule of protein, to establish that the chymopapain A molecule contains, in addition, one non-essential thiol group per molecule and to recalculate the literature value of epsilon 280 for the enzyme as 36 000 M-1 X cm -1. The Michaelis parameters for the hydrolysis of L-benzoylarginine p-nitroanilide and of benzyloxy-carbonyl-lysine nitrophenyl ester at 25 degrees C, and I 0.1 at several pH values catalysed by chymopapain A, papaya proteinase omega, papain (EC 3.4.22.2) and actinidin (EC 3.4.22.14) were determined. Towards these substrates chymopapain A has kcat./km values similar to those of actinidin and of papaya proteinase omega and significantly lower than those of papain or ficin. The environment of the catalytic site of chymopapain A is markedly different from those of other cysteine proteinases studied to date, as evidenced by the pH-dependence of the second-order rate constant (k) for the reaction of the catalytic-site thiol group with 2,2'-dipyridyl disulphide. The striking bell-shaped component that is a characteristic feature of the reactions of S-/ImH+ (thiolate/imidazolium) ion-pair components of many cysteine-proteinase catalytic sites with the 2,2'-dipyridyl disulphide univalent cation is not present in the pH-k profile for the chymopapain A reaction. The result is consistent with the presence of an additional positive charge in, or near, the catalytic site that repels the cationic form of the probe reagent. Resonance Raman spectra were collected at pH values 2.5, 6.0 and 8.0 for each of the following dithioacyl derivatives of chymopapain A: N-benzoylglycine-, N-(Beta-phenylpropionl)glycine- and N-methoxycarbonylphenylalanylglycine-. The main conclusion of the spectral study is that in each case the acyl group binds as a single population known as conformer B in which the glycinic N atom is in close contact with the thiol S atom of the catalytic-site cysteine residue, as is the case also for papain and other cysteine proteinases studied. Thus the abnormal catalytic-site environment of chymopapain A detected by the reactivity-probe studies, which may have consequences for the acylation step of the catalytic act, does not perturb the conformation of the bound acyl group at the acyl-enzyme-intermediate stage of catalysis.
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PMID:Chymopapain A. Purification and investigation by covalent chromatography and characterization by two-protonic-state reactivity-probe kinetics, steady-state kinetics and resonance Raman spectroscopy of some dithioacyl derivatives. 351 53

Fifty consecutive patients treated with chymopapain injection for a clinical and radiographic diagnosis of herniated nucleus pulposus were evaluated prospectively. All patients had a prechymopapain computed tomography (CT) scan and a three-month postinjection CT scan. In addition, ten patients (20%) had a six-month postinjection CT scan. All scans were interpreted blindly. Only six patients (12%) had obvious changes in the size of the disc when preinjection and three-month postinjection CT scans were compared. By six months, however, seven of ten patients (70%) had obvious changes in their CT scan. Seven patients (14%) were considered chymopapain treatment failures and were later treated with surgical discectomy. Only two of these seven patients (30%) had obvious changes in their three-month CT scan. Chymopapain injection did not alter the size of the herniated portion of the disc during the first three months after chymopapain injection. A decision to operate for presumed chymopapain failure should therefore be based on clinical grounds, rather than on the three-month CT appearance of the herniated disc.
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PMID:Computed tomography scanning after chymopapain injection for herniated nucleus pulposus. A prospective study. 358 60

With Magnetic Resonance Imaging (MRI) it is possible to monitor the changes in water content of the nucleus pulposus after intradiscal injection of chymopapain. In this prospective study the changes that occurred in 20 patients undergoing single-level chemonucleolysis were monitored. A constant pattern of gradual reduction of nuclear signal was seen in all cases. Complete loss of signal took at least 6 weeks and corresponded to the maximum reduction in disc space height. Seventeen patients were scanned at more than 1 year after treatment. Of these, 13 had been treated by chemonucleolysis alone. No significant return of signal from the nucleus pulposus was noted despite a slight reconstitution in disc space height. Chymopapain produced irreversible changes analogous to gross premature disc degeneration. No similar changes were noted in a control group of 12 patients (31 discs) undergoing diagnostic discography without injection of the enzyme.
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PMID:The long-term effect of chemonucleolysis on the intervertebral disc as assessed by magnetic resonance imaging. 368 22

Fifty consecutive patients undergoing chemonucleolysis with chymopapain at William Beaumont Hospital were analyzed with special reference to the following factors: the physical examination, the dye pattern noted on discogram, and the size of the preoperative myelographic defect. Discogram pattern was divided in four types: normal disc, degenerative pattern, degenerative pattern with extravasation, and annular injection. The myelograms were graded into a mild defect, a moderate defect, or a severe defect. Follow-up averaged 20 months. Conclusions of this study were Chymopapain can be considered as an alternative to lumbar laminectomy for relief of sciatica secondary to herniated disc. Statistically significant improved postinjection results were noted when patients presented with three out of four objective physical findings consisting of positive straight leg raising, reflex change, dermatomal paresthesia pattern, and/or mild motor weakness. Placement of the needle within the nucleus leads to a statistically significant improved result over placement of the needle into the annulus. A severe myelographic defect greater than 50% dura sac compression is a relative contraindication to the injection of chymopapain.
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PMID:Chemonucleolysis. The relationship of the physical findings, discography, and myelography to the clinical result. 375 74

Magnetic resonance imaging (MRI) of the spine produces images which reflect the chemical composition of the intervertebral disc. We have conducted a prospective study of the serial changes in the MRI appearance of the intervertebral disc after chemonucleolysis with the enzyme chymopapain. Fourteen patients were studied after single-level chemonucleolysis and the results compared with a control group of 17 discs in six patients who had diagnostic discography without enzyme insertion. A consistent pattern of gradual loss of signal from the nucleus pulposus culminating in complete loss of nuclear signal was seen in all cases after chemonucleolysis. Chymopapain therefore produced MRI changes analogous with premature gross disc degeneration. The rate at which this occurred varied; complete loss of signal took at least six weeks. Transitory minor end-plate changes were present in five patients, probably representing a mild chemical discitis. No similar changes were seen in the discography group.
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PMID:The changes in the intervertebral disc after chemonucleolysis demonstrated by magnetic resonance imaging. 378 31

Although infection following intradiscal injections has been recognized as a distinct entity, discitis following chemonucleolysis has been often attributed to a chemical reaction from chymopapain. In the first part of this study the effect of chymopapain and Conray 280 on a wide range of bacteria was measured in vitro. Chymopapain was found to have a bactericidal effect on all bacteria tested, which was more pronounced with gram positive organisms, whereas Conray 280 showed very little if any antibacterial effect after 48 hours. The aim of the second part of the study was to test the hypothesis that discitis following intradiscal chymopapain injection is due to infection and not to a chemical reaction. Multiple level lumbar intradiscal injections were carried out in eight mature sheep. Sixteen discs in four sheep were injected with a mixture of reconstituted chymopapain and a Staphylococcus epidermidis suspension. Sixteen discs in another four sheep were injected with reconstituted chymopapain only. All sheep were sacrificed at 6 weeks and the discs and end-plates were examined radiologically, and by histopathology and nuclear material was cultured for bacteria. None of the controls showed any evidence of discitis, whereas all sheep injected with bacteria had typical radiologic and histopathologic changes of discitis. However, in most cases in which end-plate lesions were well established there was no evidence of bacteria at sacrifice. These findings support the opinion that discitis following intradiscal injection is always due to infection introduced by the needle tip.
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PMID:Discitis following chemonucleolysis. An experimental study. 378 39

A study has been made of the mechanism of action of intradiscal injections of preparations of chymopapain in the treatment of sciatica. Such preparations were found to contain at least four distinct proteins, but enzymatically active chymopapain was the component mainly responsible for releasing glycosaminoglycan from cartilaginous tissue. Previous suggestions that an electrostatic interaction between chymopapain and glycosaminoglycan is important to the action of injected enzyme were not supported by the finding that both positively and negatively charged forms of chymopapain efficiently released glycosaminoglycan from cartilaginous tissue. In contrast, cysteine alone did not cause release of glycosaminoglycan. Chymopapain was found to be inhibited efficiently by the protein inhibitors, cystatin C and low molecular weight kininogen in vitro, and the possible relevance of this finding to the efficacy and safety of chemonucleolysis is discussed.
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PMID:The biochemistry of the action of chymopapain in relief of sciatica. 378 40

Chymopapain, a cysteine protease of papaya latex, has been purified with the use of fast protein liquid chromatography. Two homogeneous fractions were analyzed for thiol content and thiol reactivity. It was found that peak 1 and peak 2 contained two and three thiol groups, respectively, per mole of enzyme. This result is inconsistent with the general belief that chymopapain contains one essential and one nonessential thiol group and suggests that a significant portion of the thiol groups was oxidized in the previous preparations. Such an oxidation can account for some of the inconsistent results reported in the literature. An irreversibly oxidized nonessential thiol group may modify the catalytic function of chymopapain especially if it is close to the active site. That one thiol group resides indeed in the vicinity of the essential thiol group is clearly demonstrated by the biphasic reactions of chymopapain with disulfide compounds such as 2,2'-dipyridyl disulfide and 5,5'-dithiobis(2-nitrobenzoate). In the first step of these reactions a mixed disulfide is formed between the enzyme and the reactant, which is followed by a first-order, intramolecular reaction leading to the liberation of the second half of the disulfide compound. Furthermore, on addition of one Hg2+ ion, 2 mol of thiol group, one essential and one nonessential, disappears concomitantly. Formation of a disulfide bond between the catalytically competent thiol group and another free thiol group of chymopapain under physiological conditions may be of regulatory importance.
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PMID:Disulfide bond formation between the active-site thiol and one of the several free thiol groups of chymopapain. 380

Chemonucleolysis with Chymopapain (Chymodiactin, Disease) bears the risk of unpredictable anaphylactic reactions. The rate of anaphylaxis is reported to be between 0.35 and 1.5%. Serological in vitro tests such as RAST (Radio Allergo Sorbent Test) or ChymoFAST (Fluorescent Allergo Sorbent Test) are used to determine increased specific IgE antibody titres against chymopapain in patients submitted to chemonucleolysis for lumbar disc disease. Alternatively skin prick tests have also been applied in clinical trials. A skin prick test including Discase, Chymodiactin and Solutrast 250 M, which is a radiopaque dye used for discography, has been performed in a total of 208 patients. One-hundred and seventy-seven patients were tested before, 31 patients were tested after chemonucleolysis with chymopapain. From the group tested before chemonucleolysis, 2.3-3.5% had positive skin testes. After chemonucleolysis, the overall allergy rate to chymopapain increased to 41.9%. Positive skin reactions seem to be time-dependent: Between the 3rd and 12th week after chemonucleolysis more than 70% of the patients had positive skin tests. There was no correlation between a history of previous allergy and the skin test result. Patients with positive skin tests should be excluded from chemonucleolysis. This procedure increases the safety for patients submitted to chemonucleolysis. No anaphylactic reaction has been observed hitherto in nearly 350 patients who were treated with the intradiscal injection of chymopapain following a negative skin prick test.
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PMID:[Chymopapain allergy. Diagnostic value of a skin test before and after chemonucleolysis]. 388 96


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