Title
Clearance of the heavy and light polypeptide chains of human tissue-type plasminogen activator in rats
Author
Gaubius instituut TNO
Rijken, D.C.
Emeis, J.J.
Publication year
1986
Abstract
In order to assess which part of the tissue-type plasminogen activator (t-PA) molecule should be (genetically) modified to obtain more-slowly-clearing mutants, two-chain t-PA and its isolated heavy and light chains were radiolabelled and injected into rats. The vast majority of t-PA and the heavy chain disappeared from the blood circulation with half-lives of 2.3 and 1.0 min respectively. The clearance of the light chain was biphasic, owing to complex-formation with plasma proteinase inhibitors. The disappearance of di-isopropylphospho-light chain, which has a blocked active site, was nearly monophasic, with a half-life of 5.7 min. Organ distribution studies showed that hepatic clearance constituted the major pathway in all cases. These results strongly suggest that t-PA is recognized by the liver primarily through the heavy chain. Chemicals/CAS: plasminogen activator, 9039-53-6; Peptides; Tissue Plasminogen Activator, EC 3.4.21.68
Subject
Animal
Binding Sites
Chromatography, Gel
Half-Life
Male
Peptides
Rats
Rats, Inbred Strains
Support, Non-U.S. Gov't
Tissue Distribution
Tissue Plasminogen Activator
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TNO identifier
230107
ISSN
0264-6021
Source
Biochemical Journal, 238 (238), 643-646
Document type
article