Regulation of the activity of lysosomal cysteine proteinases by pH-induced inactivation and/or endogenous protein inhibitors, cystatins

Biol Chem Hoppe Seyler. 1995 Apr;376(4):225-30. doi: 10.1515/bchm3.1995.376.4.225.

Abstract

The kinetics of pH-induced inactivation of human cathepsins B and L was studied by conventional and stopped-flow methods. The inactivation of both enzymes was found to be an irreversible, first-order process. The inactivation rate constants increased exponentially with pH for both enzymes. From log kinac vs pH plots, 3.0 and 1.7 protons were calculated to be desorbed for pH-induced inactivation of cathepsins L and B. Cathepsin B was thus substantially more stable than cathepsin L (approximately 15-fold at pH 7.0 and 37 degrees C). Cathepsin B was efficiently inhibited by cystatin C at pH 7.4, whereas the inhibition by stefin B and high molecular weight kininogen was only moderate. In contrast, cathepsin L was efficiently inhibited by both chicken cystatin and stefin B at this pH kass approximately 3.3 x 10(7) m-1 s-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsin B / antagonists & inhibitors
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors
  • Chickens
  • Cystatins / physiology*
  • Cysteine Endopeptidases / metabolism*
  • Endopeptidases*
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Lysosomes / enzymology*

Substances

  • Cystatins
  • Cathepsins
  • Endopeptidases
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L
  • cathepsin S