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Living organisms possess different systems of biological amplification that help them achieve a fast response to a given stimulus in substrate cycling [1][2][3], enzyme cascades [4,5] and limited proteolysis reactions [6][7][8][9]. Limited proteolysis is an irreversible and exergonic reaction under normal physiological conditions, and there is no opposite reaction that regenerates the same hydrolyzed peptidic bond or that reinserts the corresponding released peptide. Proenzyme activation therefore is a control mechanism that differs essentially from allosteric transitions and reversible covalent modifications.Proenzyme activation by proteolytic cleavage of one or more peptide bonds requires the presence of an activating enzyme. In those cases in which the activating enzyme is the same as the activated one, the proenzyme activation process is termed autocatalytic. Physiological examples include the activation of trypsinogen into trypsin [10,11], the conversion of pepsinogen into pepsin [12][13][14], and prekallikrein into kallikrein [15,16].Several reports describe the kinetic behaviour of enzyme systems involving autocatalytic zymogen activation -with or without steps in rapid equilibrium conditions -in the presence [17] and absence [18] of a substrate of the enzyme to monitor the reaction through the release of product, and also in the presence of an inhibitor of the enzyme [19,20]. In all of these contributions, the zymogen was considered to be without enzyme activity. Nevertheless, references to the enzyme activity of zymogens are increasingly more frequent [21][22][23]. A mathematical description was made of an autocatalytic zymogen activation mechanism involving both intra-and intermolecular routes. The reversible formation of an active intermediary enzyme-zymogen complex was included in the intermolecular activation route, thus allowing a Michaelis-Menten constant to be defined for the activation of the zymogen towards the active enzyme. Time-concentration equations describing the evolution of the species involved in the system were obtained. In addition, we have derived the corresponding kinetic equations for particular cases of the general model studied. Experimental design and kinetic data analysis procedures to evaluate the kinetic parameters, based on the derived kinetic equations, are suggested. The validity of the results obtained were checked by using simulated progress curves of the species involved. The model is generally good enough to be applied to the experimental kinetic study of the activation of different zymogens of physiological interest. The system is illustrated by following the transformation kinetics of pepsinogen into pepsin.

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