Base-Catalyzed Feedback in the Urea−Urease Reaction

Abstract

The bell-shaped rate-pH curve coupled to production of base in the urea-urease reaction was utilized to give feedback-driven behavior: an acid-to-base pH clock (a kinetic switch), bistability and hysteresis between an acid/base state when the initial pH was adjusted by a strong acid, and aperiodic pH oscillations when the initial pH was adjusted by a weak acid in an open reactor. A simple model of the reaction reproduced most of the experimental results and provided insight into the role of self-buffering in the dynamics. This reaction suggests new possibilities in the development of biocompatible feedback to couple to pH-sensitive processes for bioinspired applications in medicine, engineering, or materials science.

Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction

“…If the initial pH value is low (pH≈4), a slow increase in pH occurs, followed by a rapid conversion to the high‐pH state (pH≈9), because the formation of ammonia leads to an increase in the rate of production of ammonia. The induction period of the reaction can be taken as the time for the reaction to reach pH 7 and has a well‐defined dependence on the initial concentrations of urease, urea, and acid, as well as the temperature 20. The reaction displays useful features inherent to autocatalytic reactions, including the ability to respond to a small amount of base with a transition from the low‐pH “off” state to the high‐pH “on” state, and the potential for oscillations and propagating pH fronts 21…”

Kinetics of the urea–urease clock reaction with urease immobilized in hydrogel beads

“…The mechanism of the reaction involves a Michaelis-Menten expression modified to take into account the bellshaped rate dependence on pH with a maximum at pH 7.4 [13]. In a batch reactor, the reaction produces ammonia which raises the pH and a characteristic pH ''clock'' is obtained in which the pH switches from a low to high value [12]. It is important to note, however, that feedback is not required for such a profile to occur in an acid-base reaction.…”

“…This mechanism for the design of an enzyme oscillator has been explored further in two systems with enzymes glucose oxidase [11] and urease [12]. The ureasecatalyzed hydrolysis of urea yields ammonia and carbon dioxide (reaction 1), and the ammonia causes an increase in the pH (reaction 2, pK a = 9.34):…”

“…It is most often extracted from Jack bean and has a maximum rate at pH 7.4. If this enzyme is added to a solution of acid and urea, then as ammonia is produced, a rapid switch from acid to base occurs after a controllable period of time [12]. Propagating pH fronts have been obtained in thin layers of solution in the ureaurease reaction and bistability and oscillations were observed in an open flow reactor under certain conditions [10].…”

Ester hydrolysis: Conditions for acid autocatalysis and a kinetic switch

“…A low conversion state can be maintained under open conditions when the production of acid is counterbalanced by outflow of acid. 19 Then a kinetic switch that responds to changes substrate is possible. For these open systems, conditions could be sought in which the rate of hydrolysis is sufficiently slow to allow the ester to fully dissolve, for example under neutral conditions, before significant changes in pH occur.…”