Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor.

作者: K.J. Frommherz , B. Faller , J.G. Bieth

DOI: 10.1016/S0021-9258(18)98623-0

关键词: Molecular biologyHeparinChondroitin sulfateBiochemistryChemistryElastaseDermatan sulfateNeutrophil elastasePancreatic elastaseCathepsin GEnzyme inhibitor

摘要: Heparin depresses the second-order rate constant ka for inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. High molecular mass heparin decreases from 1.3 x 10(7) M-1 s-1 to a limit 4.6 10(4) s-1. Low is about 7-fold less effective. Dermatan sulfate and chondroitin are efficient. preparations used in clinical care also strongly depress when tested at concentrations corresponding their efficacy. elastase/eglin c cathepsin G/alpha inhibitor systems but not that inhibitor/pancreatic or trypsin pairs. These results, together with Sepharose-heparin binding studies, indicate ka-depressing effect polymer related its ability form tight complex One mol high binds 3 Kd 3.3 nM. 1:1 stoichiometry 89 For both heparins lowest fully saturated heparin. From this we conclude ka, because heparin-elastase able slowly react dissociates complex. findings may have important pathophysiological bearing.

参考文章(45)
Gregory R. Schonbaum, Burt Zerner, Myron L. Bender, The Spectrophotometric Determination of the Operational Normality of an α-Chymotrypsin Solution Journal of Biological Chemistry. ,vol. 236, pp. 2930- 2935 ,(1961) , 10.1016/S0021-9258(19)76404-7
K H Duswald, M Jochum, H Fritz, W Schramm, Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery. Surgery. ,vol. 98, pp. 892- 899 ,(1985)
Robert P. Mecham, Regulation of matrix Accumulation ,(1986)
Theodore Chase, Elliott Shaw, p-Nitrophenyl-p′-guanidinobenzoate HCl: A new active site titrant for trypsin☆ Biochemical and Biophysical Research Communications. ,vol. 29, pp. 508- 514 ,(1967) , 10.1016/0006-291X(67)90513-X
P L Stein, A J van Zonneveld, H Pannekoek, S Strickland, Structural domains of human tissue-type plasminogen activator that confer stimulation by heparin Journal of Biological Chemistry. ,vol. 264, pp. 15441- 15444 ,(1989) , 10.1016/S0021-9258(19)84848-2
J C Powers, R Boone, D L Carroll, B F Gupton, C M Kam, N Nishino, M Sakamoto, P M Tuhy, Reaction of azapeptides with human leukocyte elastase and porcine pancreatic elastase. New inhibitors and active site titrants. Journal of Biological Chemistry. ,vol. 259, pp. 4288- 4294 ,(1984) , 10.1016/S0021-9258(17)43043-2