Heparin interferes with the inhibition of neutrophil elastase by its physiological inhibitors.
Heparin depresses the second-order rate constant kass for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. For high and low molecular weight heparin the decrease in kass is 290-fold and 40-fold, respectively. This is due to a tight binding of the polymer to elastase: Kd = 3.3 nM or 89 nM for high or low molecular weight heparin respectively. In contrast heparin increases the rate of inhibition of elastase by mucus proteinase inhibitor. For low molecular weight heparin, there is a 27-fold increase in kass. This is due to a strong binding of the polymer to the inhibitor (Kd = 50 nM) which undergoes a conformational change.
Faller
B
B
Université Louis Pasteur de Strasbourg, INSERM U 237, Laboratoire d'Enzymologie, Faculté de Pharmacie, Illkirch, France.
Frommherz
K
K
Bieth
J G
JG
D002846:Chromatography, Affinity; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011479:Protamines / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000502:physiology*
D006025:Glycosaminoglycans; D011479:Protamines; D015842:Serine Proteinase Inhibitors; D006493:Heparin; D010196:Pancreatic Elastase