Effect of prosthetic sugar groups on the pharmacokinetics of glucose-oxidase.
The administration of enzymes is of potential therapeutic value in many disease states, e.g. lysosomal storage diseases, provided problems in the metabolism and targeting of large proteins can be overcome. We have addressed ourselves to these problems by studying the pharmacokinetics and distribution of glucose-oxidase (GO) and some of its derivatives in mice. A saturable mechanism was responsible for GO uptake by mononuclear phagocytes. After construction of a pharmacokinetic model, the Kuptake (850 nmol/l) and the number of capturing cells were determined; uptake was half the initial plasma concentration in about 10 min. Deglycosylated GO's had half-lives of about 100 min and were taken up by the same organs that took up native GO. Galactosylated GO had a half-life of 4 min and a different distribution; it was taken up preferentially by the liver in hepatocytes. Our results illustrate the role sugars might play in the targeting of foreign proteins to different cell types, and the feasibility of determining in vivo microscopic constants such as the affinity between molecules and certain cells.
Demignot
S
S
Laboratoire de Technologie Enzymatique, Université de Compiègne, France.
Domurado
D
D
D000818:Animals; D001234:Aspergillus niger / Q000201:enzymology; D002241:Carbohydrates / Q000494:pharmacology*; D005949:Glucose Oxidase / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology; D051379:Mice; D008954:Models, Biological; D009504:Neutrophils / Q000201:enzymology; D010047:Ovalbumin / Q000032:analysis; D010504:Periodic Acid / Q000032:analysis; D011506:Proteins / Q000032:analysis
D002241:Carbohydrates; D011506:Proteins; D010504:Periodic Acid; D010047:Ovalbumin; D005949:Glucose Oxidase