372 7. INHIBITION IN MULTIENZYME SYSTEMS 



On the whole, although feedback systems operate more slowly than com- 

 parable linear chains, they possess a wider degree of stability in resisting 

 inhibition. 



NETWORK SYSTEMS 



If grids of transferring sites actually exist on complex enzymes or in 

 multienzyme systems, as has been postulated for the succinic and DPNH 

 dehydrogenases by Green (1956), the kinetics may be quite different than 

 those of ordinary enzyme reactions. In an electron-transferring grid, rates 

 cannot be formulated in terms of Michaelis-Menten kinetics, unless the 

 conductance is so high that electron movement through the grid does not 

 contribute to the over-all rate behavior. The mechanism of conduction 

 here, of course, is not the same as through metals but involves cyclic oxi- 

 dation and reduction of the grid components. It is quite probable that 

 such electron transfers would not be limiting under normal conditions, 

 but might become so in the presence of certain inhibitors, for example 

 those chelating metal ions in the grid. The response to inhibition would 

 have to be expressed in terms of the statistical distribution of inhibitor 

 molecules throughout the grid, but in the present state of ignorance of the 

 organization of such systems, a quantitative treatment would be meaning- 

 less. One could predict, in general, that as the concentration of inhibitor 

 was increased, there would be little effect on the conductance or rate until 

 a relatively large fraction of the sites was combined, since some pathways 

 would remain functional despite a scattering of inactive sites. However, 

 at higher inhibitor concentrations the rate will drop rapidly, so that an 

 inhibition-concentration curve will be very steep. It may also be noted 

 that combination of a grid site with an inhibitor need not block electron 

 flow through that site, but may alter the oxidation-reduction potential or 

 merely slow the rate of movement of electrons through that site. A spec- 

 trophotometric study of the changes in the steady-state conditions of the 

 respiratory enzymes in wheat roots and yeast by Lundegardh (1959) led 

 him to postulate a spatial organization of the respiratory system in which 

 the individual enzymes form multimolecular units. Cytochrome b and 

 FAD occupy one complex grid system and cytochrome c and cytochrome 

 oxidase occupy another mixed grid, the flow of electrons occurring within 

 a network in each case. 



GENERAL CONSIDERATIONS OF MULTIENZYME SYSTEMS 



There are certain general properties of multienzyme systems and several 

 concepts applicable to all types of system that will be discussed briefly in 

 this section. 



