The Generation and Transmission of Metabolic Fluxes

Metabolic pathways (or systems) consist of a series of reactions (usually catalyzed by enzymes, but also including transport systems across membranes), in which the product of one reaction (or step) is a substrate 

Here Ei - E4 denote the enzyme-catalyzed reactions and A - D represent the intermediates of the pathway (often referred to as the pathway substrates ). For reasons given later it is useful to regard such a sequence of reactions as transmitting a chemical (or metabolic) flux, with each intermediate carrying the flux between the component reactions. 

In the above example, all the reactions are nonequilibrium (i.e., kinet-ically irreversible) so that there is no significant reverse reaction at any step. However, many metabolic reactions are very close to equilibrium (i.e., kinetically reversible) and therefore have a reverse reaction (or reverse process) whose rate (o,) is only slightly less than that of the forward rate (of)  

Flux generation is needed because the steady-state is characterized by a defined rate of operation of the whole pathway in the above hypothetical system this means that reactions Ex to E4 all proceed at the same rate. For this to be possible the first reaction of the sequence (Ej) must not respond to changes in its pathway substrate concentration, [A]. If it did, the rate of Ej would decline continuously as A was consumed by the pathway, so that a constant rate of Ej and hence a steady-state would be impossible. In metabolic systems, saturation of the first reaction with its pathway substrate (denoted by the symbol, / ) produces the required insensitivity to concentration of this substrate. Reactions such as E, which are saturated with their pathway substrate, can be regarded as generating the steady-state flux and have therefore been termed fluxgenerating steps — see Newsholme and Crabtree (31). 

It should be noted that the term flux in flux-generating step refers to a steady-state flux located entirely within a tissue or an organism. It does not refer to global fluxes such as natural carbon or nitrogen cycles these are not in a steady-state. 

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