PROSPECTS FOR ADVANCING THE UNDERSTANDING OF COMPLEX BIOCHEMICAL SYSTEMS

The application of mathematical theories to understanding the behaviou r of complex biochemical systems is reviewed. Key aspects of behaviour are identified as the Bur through particular pathways in a steady sta te, the nature and stability of dynamical states, and the thermodynami c properties of systems. The first of these is dealt primarily in theo ries of metabolic control, and metabolic control analysis (MCA) is an important example. The valid application of this theory is limited to steady-state systems, and the cases where the essential features of co ntrol can be derived from calibration experiments which perturb the st ate of the system by a sufficiently small amount from its operating po int. In practice, time-dependent systems exist, it is not always possi ble to know a priori whether applied perturbations are sufficiently sm all, and important features of control may lie farther from the operat ing point than the application of the theory permits. The nature and s tability of dynamical and thermodynamical states is beyond the scope o f MCA. To understand the significance of these limitations fully, and to address the dynamical and thermodynamical properties, more complete theories are required. Non-linear systems theory offers the possibili ty of studying important questions regarding control of steady and dyn amical states. It can also link to thermodynamic properties of the sys tem including the energetic efficiency of particular pathways. However , its application requires a more detailed characterisation of the sys tem under study. This extra detail may be an essential feature of the study of non-equilibrium states in general, and non-ideal pathways in particular. Progress requires considerably more widespread integration of theoretical and experimental approaches than currently exists.