Inter-alpha-trypsin inhibitor. Inhibition spectrum of native and derived forms.
The conversion of inter-alpha-trypsin inhibitor (I alpha I) into active, acid-stable derivatives by proteolytic degradation has been tested with 10 different proteinases. Of these, only plasma kallikrein, cathepsin G, neutrophil elastase, and the Staphylococcus aureus V-8 proteinase were found to be effective, each releasing more than 50% of this activity. However, a strong correlation between inhibitor degradation and significant release of acid-stable activity could only be found with the V-8 enzyme. Inhibition kinetics for the interaction of native I alpha I, the inhibitory fragment released by digestion with S. aureus V-8 proteinase, or the related urinary trypsin inhibitor, with seven different proteinases indicated that all had essentially identical Ki values with an individual enzyme and, where measurements were possible, nearly identical second order association rate constants. Significantly, none of the five human proteinases tested, including trypsin, chymotrypsin, plasmin, neutrophil elastase, and cathepsin G, would appear to have low enough Ki values to be physiologically relevant. Thus, the role of native I alpha I or its degradation products in controlling a specific proteolytic activity is still unknown.
Potempa
J
J
Department of Microbiology and Immunology, Jagiellonian University, Cracow, Poland.
Kwon
K
K
Chawla
R
R
Travis
J
J
D000510:Alpha-Globulins / Q000302:isolation & purification / Q000502:physiology* / Q000652:urine; D056649:Cathepsin G; D002403:Cathepsins; D004347:Drug Interactions; D010450:Endopeptidases; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007610:Kallikreins; D007700:Kinetics; D008970:Molecular Weight; D010196:Pancreatic Elastase; D012697:Serine Endopeptidases; D014361:Trypsin Inhibitors / Q000302:isolation & purification / Q000502:physiology* / Q000652:urine
D000510:Alpha-Globulins; D014361:Trypsin Inhibitors; C011877:inter-alpha-inhibitor; D002403:Cathepsins; D010450:Endopeptidases; D007610:Kallikreins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; C032923:microbial serine proteinases