Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potential therapeutic usefulness of administered enzymes is limited by toxicity and allergenicity. To overcome these problems we are using scurvy to test various enzyme modifications that may be suitable for therapy. L-Gulonolactone oxidase, which catalyzes the final step in ascorbic acid biosynthesis, is immunoprecipitated with specific antisera from rabbits and then cross-linked with glutaraldehyde. The modified enzyme retains activity sufficient to elicit ascorbic acid synthesis in scorbutic guinea pigs. Intraperitoneal injection of this altered enzyme to animals supplemented with L-gulonolactone increases plasma concentrations of the vitamin. Importantly, multiple doses of the complex are tolerated. Therefore, it is possible to prolong survival time of animals fed an ascorbic acid-deficient diet by this enzyme replacement therapy. This procedure can also be applied to other enzymes that have potential therapeutic use. Serum cholinesterase and asparaginase both retain activity after this modification and are tolerated in single or in weekly repeated injections. Following three or four weekly injections, an anaphylactic reaction to serum but not to enzyme can be elicited if they are injected intravascularly. We conclude that the stability of the immobilized foreign enzyme is a critical factor in lessening the toxicity to multiple injections of these foreign proteins.
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PMID:Heterologous immunoprecipitates also have potential for therapeutic use. 310 56

Benzoyl- and isopentenoyl phosphoric triamides (BPA and IPA) strongly inhibited urease activities from jack bean, soybean, watermelon seed, Proteus mirabilis, P. rettgeri, P. vulgaris, Mycobacterium smegmatis, and Ureaplasma urealyticum. Their I50 values (the final concentration causing 50% inhibition), independent of enzyme source, were 2-21 nM, which are about 1,000-fold lower than that of caprylohydroxamic acid, one of the most potent urease inhibitors. ATP-urea amidolyase activity was inhibited 50% by BPA at a higher concentration of 0.28 mM, but was not affected by IPA even at 1.3 mM. Thirteen kinds of hydrolases (trypsin, chymotrypsin, thermolysin, leucine aminopeptidase, papain, lipase, alpha-amylase, glucuronidase, asparaginase, arylsulfatase, alkaline phosphatase, acid phosphatase, and true cholinesterase), two oxidoreductases (catalase and alcohol dehydrogenase), three transferases (glutamic-oxaloacetic aminotransferase, gamma-glutamyl transpeptidase, and arylsulfotransferase) and two kinases (pyruvate kinase and creatine kinase) were not affected at all even at 1 mM BPA and IPA. Exceptionally, pseudo-cholinesterase from human serum was inhibited by BPA and IPA, whose I50 values were 70 nM and 10 muM, respectively, using acetylthiocholine as a substrate. These values increased to 0.55 muM and 54 muM, respectively, when acetylcholine was used as a substrate. These results show that N-acylphosphoric triamides potently and specifically inhibit urease activity at concentrations of nM order.
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PMID:Specific inhibition of urease by N-acylphosphoric triamides. 384 42

Studies were carried out to assess the prospects of adapting an enzyme administration procedure developed with rat liver gulonolactone oxidase to other enzymes of therapeutic interest. The enzyme is administered intraperitoneally as the glutaraldehyde-reacted immunoprecipitate. A gulonolactone oxidase from a different source, chicken kidney, also shows catalytic capability following administration. This finding suggests that other enzymes modified by this procedure might also act in vivo. Four out of five enzymes tested (asparaginase, serum cholinesterase, rat and chicken gulonolactone oxidases) have significant catalytic activity and relatively minor changes in affinity for substrate after the modification, and only one (histidase) is inactivated by the modification. Analysis of immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of these enzymes indicates that they consist largely of enzyme and immunoglobulin G. All five of these modified enzymes are not toxic even with repetitive administrations whereas unmodified asparaginase is allergenic to a majority of guinea pigs tested. The modification described is very simple and rapid and is, therefore, a practical means of preparing certain enzymes for therapeutic administration.
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PMID:Adaptability of an enzyme replacement therapy to other enzymes with potential therapeutic applications. 409 51