The disappearance of enzyme-inhibitor complexes from the circulation of man.
1. Complexes of human trypsin and human granulocyte elastase with alpha1-anti-trypsin and alpha2-macroglobulin were isolated and injected intravenously into human volunteers. 2. The elimination of alpha2-macroglobulin complexes with trypsin and elastase followed single-exponential functions with half-lives of 9 and 12 min respectively. The complexes showed no tendency to dissociate. 3. Complexes of alpha1-anti-trypsin with trypsin persisted in the circulation much longer, with a half-life of 3-5 h; complexes of alpha1-anti-trypsin with elastase had an intermediate half-life of 1 h. 4. Dissociation was observed of alpha1-anti-trypsin complexes with transfer of trypsin and elastase to alpha2-macroglobulin. 5. Dialysable radioactivity appeared in the urine soon after the injection of alpha2-macroglobulin complexes, which suggested a breakdown of complexes by cells in the reticuloendothelial system. Radioactivity over the liver achieved maximum values within 30-40 min after the injection of alpha2-macroglobulin complexes but not until 50-70 min after the injection of alpha1-anti-trypsin comlexes. 6. These results support the concept of a key position for alpha2-macroglobulin in the protective mechanisms against endogenous proteases.
D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D010196:Pancreatic Elastase / Q000097:blood*; D011485:Protein Binding; D014357:Trypsin / Q000097:blood*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D010196:Pancreatic Elastase; D014357:Trypsin