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HE Fuchs, H Berger and SV Pizzo
The catabolism of human tissue plasminogen activator (t-PA) was studied in
mice. The clearance of t-PA labeled with iodine 125 was rapid (t1/2). The
clearance of phenylmethylsulfonyl-125I-t-PA, which is active
site-inhibited, was identical to the active enzyme. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the vast
majority of 125I-t-PA injected into the circulation was present as free
enzyme and not in a complex with inhibitors. The clearance of 125I-t-PA was
unaltered by large molar excesses of several ligands of known clearance
specificities, including macroalbumin, asialoorosomucoid, and
diisopropylphosphorylthrombin and was also not altered in the presence of a
1,000-fold molar excess of unlabeled t-PA. Organ distribution studies
demonstrated that the early rapid clearance of 125I-t-PA occurred in
hepatocytes, followed by a later renal phase of clearance. The clearance of
125I-urokinase (UK) also was studied and was very similar in all aspects to
the clearance of 125I-t-PA. These results suggest that both t-PA and UK are
cleared from the circulation by unique nonsaturable processes localized in
the liver that are independent of the proteinase active site.
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| Copyright © 1985 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||