EFFECT OF CHANNELING ON THE CONCENTRATION OF BULK-PHASE INTERMEDIATESAS CYTOSOLIC PROTEINS BECOME MORE CONCENTRATED

This paper shows that metabolic channelling can provide a mechanism fo r decreasing the concentration of metabolites in the cytoplasm when cy tosolic proteins become more concentrated. A metabolic pathway in whic h two sequential enzymes can form a dynamic complex catalysing the dir ect transfer of an intermediate is compared with the analogous pathway lacking a channel (an 'ideal' pathway). In an ideal pathway a proport ional increase in protein content does not result in a change in the s teady-state concentration of the bulk-phase intermediate, whereas in a channelling pathway the bulk-phase intermediate either decreases or i ncreases depending on the elemental rate constants within the enzyme m echanisms. When the concentrations of the enzymes are equal, the pool size decreases with increasing protein concentration if the elemental step depleting the bulk-phase intermediate exerts more control on its concentration than the step supplying the intermediate. Results are il lustrated numerically, and a simplified dynamic channel is analysed in which the concentration of the enzyme-enzyme complex is negligible co mpared with the monomeric enzyme forms. For such a 'hit-and-run' chann el it is shown that, when the product-releasing step of the enzyme loc ated upstream is close to equilibrium, the pool size decreases as the concentrations of the enzymes increase in proportion, regardless of th e rate, equilibrium constants and concentration ratios of the two sequ ential enzymes.