GENERAL CONSIDERATIONS OF MULTIENZYME SYSTEMS 375 



This system may now be extended to the situation where B is being formed 

 enzymically at a constant rate from A: 



In the steady state: 



Ej Eg 



A^ B,^ B,^ C (7-61) 



(7-62) 



(A) + K, (B), + K, 



from which the value of (B)2 may be obtained in terms of (A). Since the 

 rate is also that given in Eq. 7-58, the value of (B)i may be calculated 

 from (B)^: 



(i 



•"■■•"■'^wItt*' 



(7-63) 



It is quite possible, however, that the rate of reaction 1 may be too rapid 

 to allow diffusion of B at a rate necessary to maintain reaction 2 in a steady 

 state with reaction 1, since, although B will accumulate, in many systems 

 (B)i cannot rise above a limited value. In such diffusion-limited multi- 

 enzyme systems, inhibition of E^ will not affect the formation of C to any 

 extent until the rate of reaction 1 has been reduced to a level comparable 

 to the diffusion process. Inhibition of Eg will generally depress formation 

 of C but the rate will progressively increase as B accumulates. 



It is likely that in the cell, where distances between enzymes are small, 

 diffusion is seldom a limiting factor in metabolic rates, unless the consec- 

 utive enzymes are separated by some barrier membrane slowing diffusion. 

 However, in isolated enzyme preparations, diffusion may well be an im- 

 portant rate-determining process, the enzymes usually being diluted and 

 relatively far apart. The opportunity for diffusion to become important 

 is increased as the size of the diffusing intermediate molecule is increased. 

 Many interenzyme diffusing molecules are quite large, such as ATP or 

 DPNH, and in isolated preparations carriers as large as cytochrome c 

 may be compelled to diffuse. 



The diffusion law applied above (Eq. 7-58) may not be valid for 

 systems where the distances involved are of molecular dimensions. A mol- 

 ecule does not diffuse in a straight line but along a complex path deter- 

 mined by collisions with other molecules. The average speed along a single 

 linear path between collisions is high but the rate of diffusion is much slower 

 due to the circuitous path taken. If the active sites of two consecutive en- 

 zymes are separated by distances of the order of 10-200 A and in a cavity 

 where no water molecules are present, the time required for transfer of an 

 intermediate between sites may be exceedingly brief. The mean speed of a 

 molecule along a linear path is given by t; = (8i?T/7rM) - and for a molecule 

 of molecular weight of 100, v = 2.6x10* cm/sec at 37. 5^. It wovild thus 



