Catalytic activity of administered gulonolactone oxidase polyethylene glycol conjugates.
Scurvy in guinea pigs provides a convenient model of inborn metabolic disease for the investigation of enzyme therapy protocols. Gulonolactone oxidase, the enzyme in ascorbic acid biosynthesis that is missing from the scurvy-prone species, was modified by attachment of polyethylene glycol. The catalytic properties of this enzyme were affected little by the modification. Intravenous injection of this modified form of the enzyme elicited ascorbic acid synthesis in a dose-dependent manner. The modified enzyme was stabilized to incubation at 37 degrees C but was not protected from inactivation by trypsin. The circulating half-life of enzyme activity was not prolonged by this modification. Further, attachment of polyethylene glycol did neither abolish the enzyme's ability to react with preformed antibodies nor eliminate its immunogenicity.
Hadley
K B
KB
Laboratory of Biochemistry, National Cancer Institute, Bethesda, Md.
Sato
P H
PH
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002645:Chickens; D004795:Enzyme Stability; D004800:Enzymes, Immobilized / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D007106:Immune Sera; D005779:Immunodiffusion; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D050544:L-Gulonolactone Oxidase; D009928:Organ Specificity; D011092:Polyethylene Glycols / Q000008:administration & dosage; D012016:Reference Values; D013401:Sugar Alcohol Dehydrogenases / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology
D004800:Enzymes, Immobilized; D007106:Immune Sera; D011092:Polyethylene Glycols; D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid