PH-DEPENDENT HYSTERETIC BEHAVIOR OF HUMAN MYELOBLASTIN (LEUKOCYTE PROTEINASE-3)

Human myeloblastin (leucocyte proteinase 3) showed a very slow approac h to the steady-state velocity when the pH was rapidly increased from 3.2 to 7.0. The kinetic mechanism of this hysteretic process was inter preted as a slow conformational change of myeloblastin from an inactiv e form at acidic pH to the active form at neutral pH. The transition b etween the two enzyme forms could occur spontaneously in the absence o f substrates with a first-order rate constant of 0.0033 s(-1). In the presence of peptide substrates activation occurred more rapidly: the o bserved rate constant was linearly dependent upon the substrate concen tration and contained a contribution of the spontaneous as well as of the substrate-dependent process, whose second-order rate constant was characteristic of the particular substrate. This pH-dependent phenomen on of hysteresis on the part of myeloblastin, that is not manifested b y the closely related leucocyte elastase, may have a physiological con trol function during phagocytosis by damping the rate of interconversi on between enzymically inactive and active enzyme conformations.