Handling Equilibrium Processes Embedded in Metabolic Systems

Thermodynamic constraints are essential for understanding the behaviour of living systems, but they are far from sufficient, because they allow a wide range of possibilities. Additional constraints imposed by kinetic considerations are often crucial in determining not merely whether a process can occur, but whether it does. Entropies of activation are in principle very useful for analysing experimental properties, but in practice they are rendered almost useless by the impossibility of estimating them accurately from observations spread over a narrow temperature range. Such estimation typically involves extrapolating more than 10-times the range of the data, and involves huge errors. Another common problem in the literature, results from confusion between actual and standard Gibbs energies of reaction: supposedly unfavourable equilibrium constants can suggest that processes necessary for life, such as reduction of sulphate by organisms that use sulphate as a terminal electron acceptor, are impossible; but as long as an organism has efficient mechanisms for maintaining reactant concentrations far from their standard states, a reaction can be driven in either direction regardless of the magnitude of its equilibrium constant. The increasing importance of computer modelling in studying metabolism has now focused attention on the question of how to handle reactions that are essentially irreversible. It has often been assumed that if the reverse reaction is negligible then all the effects of products can be neglected, but that is a potentially serious error: many enzymes are known where product inhibition has important effects on the rate of a reaction that is for practical purposes irreversible. http://www.beilstein-institut.de/bozen2004/proceedings/CornishBowden/CornishBowden.pdf