Print Email Facebook Twitter Clearance of the heavy and light polypeptide chains of human tissue-type plasminogen activator in rats 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 188.8.131.52 Subject AnimalBinding SitesChromatography, GelHalf-LifeMalePeptidesRatsRats, Inbred StrainsSupport, Non-U.S. Gov'tTissue DistributionTissue Plasminogen Activator To reference this document use: http://resolver.tudelft.nl/uuid:74bc659a-364b-4d79-a370-42f339244a16 TNO identifier 230107 ISSN 0264-6021 Source Biochemical Journal, 238 (238), 643-646 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.