TRANSITION BETWEEN STEADY STATES 389 



Examples of Transition between Steady States 



In most instances it is difficult to determine the transition time or the 

 exact pattern of change with time, not only because such changes are often 

 very rapid, but also due to the fact that the rate at which the inhibitor 

 exerts its effect is generally unknown. If the inhibitor acts slowly, due to 

 either permeability or kinetic factors, the meaning of transition time loses 

 its significance. However, there are in the literature many reports of the 

 establishment of a new steady state that is certainly slower than the rate 

 at which inhibition is induced, although exact determinations of these 

 rates are uncommon. Perhaps the best demonstration of the time variation 

 in intermediate concentrations is provided by the work of Chance (Chance, 

 1954; Chance and Williams, 1956) on the regenerative type electron-tran- 

 sport systems, where the state of the electron acceptors fluctuates charac- 

 teristically following inhibition. It is probable that adaptive phenomena are 

 often examples of such a transition, exiDressed at the cellular level in function- 

 al or growth changes. Hinshelwood (1946) has interpreted bacterial adapta- 

 tion to inhibitors, such as proflavine, in terms of steady-state processes, 

 wherein, however, the concentrations of enzymes may also change. The 

 best examples of overshoot are not from inhibitor studies but in the rapid 

 changes resulting from a sudden increase in pressure. The rate of beating 

 of frog heart cells in tissue culture (Landau and Marsland, 1952) and of 

 Mytilus gill cilia (Pease and Kitching, 1939) is increased by a sudden pres- 

 sure rise but rapidly returns to normal; in the former case, pressures of 

 10,000 psi can be achieved in steps with the rate returning to normal in 

 each case, and this can best be understood in terms of transitions between 

 steady states, even though we are ignorant of the fundamental reactions 

 that are involved. A similar example, more directly related to enzyme 

 systems, would be bioluminescence: a high intensity "flash" is caused by 

 a sudden rise in pressure while a "black-out" results from rapid pressure 

 release (Fig. 7-42) (Brown et al., 1942). There is a need for a more quanti- 

 tative kinetic approach to the responses of enzyme systems and cells to 

 inhibitors because the over-all effects of inhibition must depend in many 

 cases on the rates at which metabolic activity is altered and new steady 

 states reached. A common example of metabolic transition is the Pasteur 

 reaction and useful information as to the exact mechanism might be pro- 

 vided by determinations of the rates at which glycolysis changes in res- 

 ponse to pOa alterations or the action of cyanide. Such an approach has 

 been initiated in the excellent work of Lynen (1958), where the time var- 

 iation of the hexosephosphates, adenine nucleotides, and inorganic phos- 

 phate following inhibition by cyanide and 2,4-dinitrophenol in yeast has 

 been determined and the establishment of new steady states demonstrated. 

 The oxygen uptake and ATP levels of Chlorella vary in a very interesting 

 fashion when glucose is suddenly added or the metabolic conditions are 



