Heparin modulation of human plasma kallikrein on different substrates and inhibitors

Heparin modulation of human plasma kallikrein on different substrates and inhibitors

Author Gozzo, Andrezza Justino Autor UNIFESP Google Scholar
Nunes, Viviane A. Autor UNIFESP Google Scholar
Cruz-Silva, Ilana Autor UNIFESP Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Faljoni-Alario, Adelaide Google Scholar
Sampaio, Misako U. Autor UNIFESP Google Scholar
Araujo, Mariana S. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract The interplay of different proteases and glycosaminoglycans is able to modulate the activity of the enzymes and to affect their structures. Human plasma kallikrein ( huPK) is a proteolytic enzyme involved in intrinsic blood clotting, the kallikrein-kinin system and fibrinolysis. We investigated the effect of heparin on the action, inhibition and secondary structure of huPK. the catalytic efficiency for the hydrolysis of substrates by huPK was determined by Michaelis-Menten kinetic plots: 5.12 x 10(4) M-1 S-1 for acetyl-Phe-Arg-p-nitroanilide, 1.40 x 10(5) M-1 S-1 for H-D-ProPhe-Arg-p-nitroanilide, 2.25 x 10(4) M-1 S-1 for Abz-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Ser-Arg-Gln-EDDnp, 4.24 x 10(2) M-1 S-1 for factor XII and 5.58 x 10(2) M-1 S-1 for plasminogen. Heparin reduced the hydrolysis of synthetic substrates ( by 2.0-fold), but enhanced factor XII and plasminogen hydrolysis ( 7.7- and 1.4-fold, respectively). the second-order rate constants for inhibition of huPK by antithrombin and C1-inhibitor were 2.40 x 10(2) M-1 S-1 and 1.70 x 10(4) M-1 S-1, respectively. Heparin improved the inhibition of huPK by these inhibitors ( 3.4- and 1.4-fold). Despite the fact that huPK was able to bind to a heparin-Sepharose matrix, its secondary structure was not modified by heparin, as monitored by circular dichroism. These actions may have a function in the control or maintenance of some pathophysiological processes in which huPK participates.
Keywords antithrombin
C1-inhibitor
factor XII
glycosaminoglycans
plasminogen
synthetic substrates
Language English
Date 2006-08-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 387, n. 8, p. 1129-1138, 2006.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 1129-1138
Origin http://dx.doi.org/10.1515/BC.2006.139
Access rights Closed access
Type Article
Web of Science ID WOS:000240351400016
URI http://repositorio.unifesp.br/handle/11600/29086

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