12] Covalently interconvertible enzyme cascade systems

Abstract

Publisher Summary This chapter reviews that the cyclic cascade systems are fundamentally different from the irreversible, unidirectional cascades of proteolytic enzymes of the blood clotting type and complement fixation. When triggered by an appropriate alarm signal the unidirectional cascade responds in an explosive manner to produce an avalanche of product needed to meet a specific biological emergency, but having fulfilled its function, the cascades are terminated by a self-destructive process that is initiated by autoregulatory signals. In effect, unidirectional cascades are contingency systems that function as biological ON-OFF switches in response to occasional emergency needs. The chapter also discusses the concepts that emerge, regarding cyclic cascades, as revealed by the simplified model. The capacity of biological systems to take advantage of the elegant regulatory mechanisms depends on the kinetic constraints, such as the concentrations and turnover numbers of the cascade enzymes and the dissociation constants of the effector–enzyme and enzyme–enzyme complexes. The kinetic analysis of the multicyclic cascade shows that, with reasonable parameters as stated above, a 50% modification of the second and third interconvertible enzymes in a three-cycle cascade can be accomplished in the millisecond time range. Further kinetic analysis shows that interconvertible enzyme cascade can in fact function as a rate amplifier to generate an almost explosive increase in enzymic activity in response to stimuli.