A computer system for analysis and modeling of multiple pathway enzyme mechanisms

• Published in: Computers in biology and medicine Vol. 7; no. 3; pp. 209 - 221
• Main Authors: Lam, Chan F., Schatz, Nancy, Priest, David
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.01.1977
• Subjects: Enzyme kinetics; Modeling; Random mechanism; Rate equations; Regression; Regression; Rate equations; Enzyme kinetics; Random mechanism; Modeling
• DOI: 10.1016/0010-4825(77)90025-7
• ISSN: 0010-4825

Due to the difficulties in deriving and solving nonlinear rate equations, enzyme kineticists often restrict their steady-state initial velocity studies to simple models which yield linear reciprocal equations. However, many enzymatic reactions yield nonlinear equations, especially when wide ranges of substrate concentration are used. Mechanisms which explain such nonlinear data include random binding and multiple site mechanisms. In addition, the rate constants are constrained according to the principle of detailed balance. Since many rate constants could appear in more than one pathway of the complex mechanism, the allowed value of these rate constants are further restricted. In this paper, techniques for deriving rate equations and constraint equations satisfying the principle of detailed balance for complex mechanisms are presented. A method to ensure that the estimated rate constants satisfy all constraint equations throughout the estimation procedure is also discussed. These techniques have been implemented on a digital computer. Rate constant estimation and results of modeling Uricase using this system are presented.