770 15. EFFECTS OF VARIOUS FACTORS ON INHIBITION 



that diffusion has a low temperature coefficient but actually some membrane 

 diffusion rates have high activation energies and are as sensitive to temper- 

 ature as are enzyme rates. This is particularly apt to be the case when the 

 diffusion is slow and can be limiting the rate of formation of some meta- 

 bolic product. 



Inhibition on the first reaction of a linear sequence will be affected 

 by temperature as described above and, since the over-all rate depends 

 only on v^ in the steady state, the over-all rate will be affected similarly. 

 If a change of the temperature, however, shifts the limiting step to another 

 reaction, the inhibition may be markedly modified. For example, if a rise 

 in temperature causes the system to leave a steady state so that reaction 2 

 controls the formation of C, an inhibition on E2 will be directly reflected 

 in d{C)ldt, whereas initially such an inhibition would not affect d{Q)jdt 

 until reaction 2 had been reduced sufficiently to be limiting. Thus tempera- 

 ture changes can alter the sensitivity to inhibition of linear enzyme systems 

 both by effects on the enzyme inhibition itself and by changes in the relative 

 rates of the reactions involved. Conversely, inhibition of a complex system 

 may alter its sensitivity to temperature variation and such changes have 

 been observed in cellular studies. 



{B) Convergent chains. In treating the system: 



A ^: E. 



■)B ^ C (15:40) 



X E3 



we come to one of the serious difficulties in the interpretation of tempera- 

 ture effects. If either of the feeding reactions to form B is speeded rela- 

 tive to the other, the rate of formation of C will be changed to a degree 

 intermediate between the changes of reaction 1 and reaction 3. If reaction 1 

 is changed by a factor of g-^ and reaction 3 by a factor of g^, since v^ = 

 v^ + '^3 in the steady state, the factor ^2 ^^Y which the formation of C is 

 changed will be given by: 



02 = , (15-41) 



Vi + V3 



For example, if i\ — 10 and Vg = 5, and a change in temperature brings 

 about changes of g^ = 2 and g^ = i in these rates, g.^ will be found to be 

 2.67. The temperature characteristics calculated from the data derived in 

 such systems will not apply to any particular enzyme reaction and will 

 be in themselves without physical meaning. Any effect of temperature on 

 V2 will not be reflected in the change of the rate of formation of C as long 

 as the system remains in a steady state, because V2 is controlled by the sum 

 of the feeding reaction rates. In cellular metabolism there are many path- 



