Metabolism of different molecular forms of adenosine deaminase intravenously infused into the rabbit.
High-Mr and monomeric adenosine deaminase were injected intravenously into the rabbit. The rates of clearance and sites of uptake of the enzymes were compared. Calf intestinal mucosa served as the source of monomeric adenosine deaminase. High-Mr enzymes were assembled in vitro from the calf enzyme and adenosine deaminase-complexing proteins isolated from rabbit plasma or kidney. An immunoassay specific for calf adenosine deaminase was used to determine which organs took up the injected enzyme. The enzymes were cleared from circulation in the following order: monomeric adenosine deaminase greater than high-Mr enzyme prepared with kidney complexing protein greater than high-Mr enzyme prepared with plasma complexing protein. High-Mr enzyme assembled with kidney complexing protein was taken up primarily by the liver. Complexing protein and adenosine deaminating activity were cleared from circulation at similar rates. This and other evidence indicate that kidney complexing protein and calf adenosine deaminase are taken up as a unit by the liver. In contrast, adenosine-deaminating activity was cleared more quickly from circulation than complexing protein in rabbits injected with enzyme prepared with plasma complexing protein. Immunoassay results indicated that calf adenosine deaminase was taken up principally by the kidney cortex and liver. Kidney was the major site of uptake of monomeric adenosine deaminase. Indirect immunoperoxidase staining was used to localize the calf enzyme in glomeruli and proximal renal tubules, the same areas in which rabbit complexing protein is localized. These results support the hypothesis that complexing proteins play a role in the clearance of adenosine deaminase from plasma [W.P. Schrader and P.J. Bryer (1982) Arch. Biochem. Biophys. 215, 107-115].
D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D005260:Female; D007263:Infusions, Parenteral; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D009700:Nucleoside Deaminases / Q000378:metabolism*; D011817:Rabbits; D013154:Spleen / Q000378:metabolism
D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase