title: Adaptability of an enzyme replacement therapy to other enzymes with potential therapeutic applications.
abstract: 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.
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000096:biosynthesis; D001215:Asparaginase / Q000097:blood / Q000627:therapeutic use; D011232:Chemical Precipitation; D002645:Chickens; D002802:Cholinesterases / Q000097:blood; D057487:Enzyme Therapy; D006638:Histidine Ammonia-Lyase / Q000627:therapeutic use; D007668:Kidney / Q000201:enzymology; D050544:L-Gulonolactone Oxidase; D013401:Sugar Alcohol Dehydrogenases / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D002802:Cholinesterases; D001215:Asparaginase; D006638:Histidine Ammonia-Lyase; D001205:Ascorbic Acid