Control of Rate of Intracellular Respiration 59 



probably important in vivo was uncovered by Lardy (1952). 

 It has been known for more than twenty years that respira- 

 tion is linked with the esterification of inorganic phosphate. 

 Using mitochondria isolated from rat liver by a procedure 

 designed to yield a preparation devoid of adenosine triphos- 

 phatase (ATPase) activity (Kielley and Kielley, 1951), 

 Lardy and Wellman (1952) were able to show that the link 

 between oxidation and phosphorylation was compulsory, i.e. 

 respiration did not occur in the absence of the components 

 necessary for oxidative phosphorylation. 



Reaction (i) must, then, be extended to include the phos- 

 phorylation reaction, thus : 



CeHiaOs + 6 O2 + 38 ADP + 38 H3PO4 -> 



6 CO2 + 44 H2O + 38 ATP (ii) 



Since cells contain only a small amount of adenosine diphos- 

 phate (ADP), respiration will stop as soon as it is all phos- 

 phorylated to adenosine triphosphate (ATP). When the cell 

 is stimulated to do work, e.g. in muscular contraction, the 

 ATP is broken down 



38 ATP + 38 H2O -> 38 ADP + 38 H3PO4 + work (iii) 



The ADP liberated in this reaction now supplies the missing 

 component on the left-hand side of equation (ii), so that 

 respiration will commence, and the ATP is resynthesized. A 

 kinetic steady state is soon set up, in which the concentration 

 of ADP, and therefore the rate of respiration, is governed by 

 the relative activities of the enzyme systems bringing about 

 reactions (ii) and (iii). 



Stimulation of respiration by ADP 



Experiments illustrating the effect of the addition of ADP 

 on the rate of respiration of rat liver mitochondria and 

 guinea-pig heart mitochondria (sarcosomes) are shown in 

 Figs. 1 and 2, respectively. In both cases, there is a sharp 

 increase in the rate of oxygen uptake on the addition of ADP, 



