New network architecture for stoichiometrically, thermodynamically and kinetically balanced metabolic reaction systems

The conventional way of assembling the metabolic reactions into networks by placing the metabolites on the nodes and associating the edges with reactions is shown to violate the mass balance, thermodynamics and kinetics. A new type of metabolic networks referred to as reaction route (RR) networks is discussed. The distinct feature of the RR networks is that both the nodes and edges are subject to mass balance, thermodynamic and kinetic constraints. To satisfy these constraints, it is necessary to introduce two different types of nodes. One of these, referred to as terminal nodes, satisfy the mass balance conditions for external metabolites. The other type of nodes, referred to as intermediate nodes, satisfy the quasi steady-state conditions for internal metabolites. It is further required that every cycle in the network be thermodynamically consistent in that the sum of affinities (Gibbs free energy changes) of the reactions comprising the cycle should add up to zero. A balanced RR metabolic network possesses a remarkable property, namely, every conceivable walk between two terminal nodes involves a sequence of metabolic reaction steps that produce an overall reaction (OR), i.e., a reaction comprising only external metabolites. A key result is that many metabolic reaction networks may be balanced if and only if the network is allowed to be infinite and periodic.