Inhibition of human liver cathepsin L by alpha 2 cysteine-proteinase inhibitor and the low-Mr cysteine proteinase inhibitor from human serum.
The inhibition of human liver cathepsin L by two specific proteinase inhibitors present in human serum, namely alpha 2 cysteine-proteinase inhibitor and the low-Mr cysteine-proteinase inhibitor, was studied. Kinetic parameters, including inhibition constants (Ki) and rate constants for association and dissociation (k+1 and K-1), were determined. The values found are consistent with a possible physiological function of these inhibitors to control cathepsin L activity. Furthermore, a transfer of active proteinase from the complex with either cysteine-proteinase inhibitor species to alpha 2-macroglobulin was demonstrated in vitro. Given the rate of dissociation of both cathepsin-L-cysteine-proteinase inhibitor complexes, a function of transitory inhibitor can therefore be hypothesized for these proteins and might then provide an explanation of the clearance of lysosomal proteinases.
D001665:Binding Sites; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D055312:Cystatin A; D015891:Cystatins; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D046911:Macromolecular Substances; D011480:Protease Inhibitors / Q000494:pharmacology*; D011506:Proteins; D013438:Sulfhydryl Compounds / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*
D055312:Cystatin A; D015891:Cystatins; D046911:Macromolecular Substances; D011480:Protease Inhibitors; D011506:Proteins; D013438:Sulfhydryl Compounds; C026407:CSTA protein, human; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L