120 Britton Chance 



the steady state characteristic of the resting muscle is re- 

 estabUshed. 



Discussion and summary 



A desirable characteristic of a respiratory control chemical 

 is that it be capable of triggering the system on and off by 

 small changes in its concentration. When this is the case, the 

 system may be set into full activity with a small increase of 

 concentration and can subside to the resting state with a small 

 decrease of concentration. Such trigger-control character- 

 istics have the advantage of preventing the accumulation of 

 large amounts of control substance prior to the complete 

 activation of the system. Poor candidates for this type of 

 control in mitochondria are phosphate, magnesium and, in 

 most cases, substrate; the system has sufficiently low affinity 

 for these substances that it cannot be triggered with low 

 concentrations. On the other hand, both ADP and calcium 

 can trigger the system at low concentrations and can stimulate 

 it to maximal activity in response to a small amount of the 

 control substance. 



High affinity for the control substance allows simultaneous 

 control of a number of processes. For example, the relatively 

 higher ADP affinity of mitochondria compared to the phos- 

 phoglucerate kinase gives the mitochondria the possibility of 

 controlling the activity of the Embden-Myerhof pathway. 

 On the other hand, the affinity of the mitochondria for phos- 

 phate is considerably lower than for ADP, and thus phosphate 

 cannot compete as effectively with phosphorylation steps in 

 glycolysis which involve this substance. Metabolic control 

 in terms of the substrate level may have the disadvantage of 

 low affinity. A further disadvantage is that substrate addition 

 to any part of an enzyme sequence may not activate the whole 

 system simultaneously. Addition of substrate would activate 

 the system in a sequence starting with those enzymes nearest 

 the substrate, since the concentration of various intermediates 

 needs to be built up; the converse is true for the expenditure 

 of substrate. In this respect, the ADP control of electron 



