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In vivo catabolism of human heparin cofactor II and its complex with thrombin

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6071789
; ;

The plasma clearance of human heparin cofactor II (HC) and its complex with thrombin (HC-T) was studied in mice and compared to the clearance of two other plasma proteinase inhibitor complexes: antithrombin III-thrombin (AT-T) and ..cap alpha.. 1-proteinase inhibitor-elastase (..cap alpha.. /sub 1/PI-E). Purified HC was labelled with /sup 125/I without loss of activity as assessed by kinetic analysis of thrombin inhibition and by ability to form a detergent-resistant complex with thrombin. /sup 125/I-HC cleared from the circulation with a t1/2 of 80 min; /sup 125/I-HC-T cleared with a t1/2 of 10 min. When coinjected, a 2500-fold molar excess of unlabelled HC-T partially blocked the clearance of /sup 125/I-HC-T (t1/2 of 53 min), suggesting the involvement of a receptor-mediated process in the catabolism of HC-T. Coinjection of a 1500-fold molar excess of AT-T also slowed the clearance of /sup 125/I-HC-T (t1/2 of 29 min); a 2000-fold molar excess of ..cap alpha.. /sub 1/PI-E further competed for /sup 125/I-HC-T recovered at autopsy was localized to the liver; similar results have been obtained for AT-T and ..cap alpha.. /sub 1/PI-trypsin.

Research Organization:
Duke Univ Medical Center, Durham, NC
OSTI ID:
6071789
Report Number(s):
CONF-870644-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BLOOD-PLASMA CLEARANCE
CATABOLISM
CLEARANCE
COAGULANTS
COMPLEXES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
IN VIVO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MAN
MEMBRANE PROTEINS
METABOLISM
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
SERINE PROTEINASES
THROMBIN
TRACER TECHNIQUES
VERTEBRATES