Conformational drift and cryoinactivation of lactate dehydrogenase

Solutions of porcine lactate dehydrogenase of micromolar concentration kept at 4 degrees C for several days lose the greater part of their enzymic activity but recover it when returned to room temperature. The rate of spoiling decreases and the rate of recovery increases with the concentration of the solutions. The decrease in tetramer stability in the cold is shown by experiments of pressure dissociation at various temperatures and confirmed because isozyme hybridization occurs in parallel with the inactivation at low temperature but is absent at room temperature. Cold-inactivated solutions contain tetramers that dissociate much more readily than those of the fully active solutions. It is postulated that cryoinactivation, like pressure inactivation, takes place through a cycle of dissociation, conformational drift [King, L., & Weber, G. (1986) Biochemistry (second paper of three in this issue)] and reassociation into inactive tetramers.