QUANTITATIVE ASPECTS OF THE CONTROL 

 OF OXYGEN UTILIZATION* 



Britton Chance 

 Johnson Research Foundation, University of Pennsylvania, Philadelphia 



A RECENT review by Lardy (1956) summarizes many 

 qualitative features of respiratory control, along lines sug- 

 gested by Loomis (1949). Now, the properties of the reaction 

 of adenosine diphosphate (ADP) and phosphate with the 

 oxidative phosphorylation system can be studied quantita- 

 tively, and the suitability of these and other substances for 

 key intermediates in metabolic control can be evaluated. We 

 shall present, in this paper, a summary of the extent to which 

 ADP and phosphate control electron transfer in mitochondria 

 isolated from a wide range of tissues. Experimental studies 

 of the effect of magnesium and calcium upon respiratory 

 control and interpretations of their possible physiological 

 function will also be given. The action of uncoupling agents 

 upon respiratory control will be considered, as will the possi- 

 bility that some uncoupling agents act selectively upon dif- 

 ferent sites of oxidative phosphorylation. Lastly, we shall 

 present experimental evidence for the intramitochondrial 

 substance responsible for respiratory control and discuss its 

 possible nature. In an effort to determine which of the possible 

 control substances determines the rate of respiration under 

 physiological conditions, we have examined intact cells and 

 tissues by optical methods that are responsive to metabolic 

 control by substrates, coenzymes, and ADP or phosphate. 



Measurement of respiratory control ratios 



It is important to define respiratory control ratio as that 

 of the respiratory rate in the presence of added ADP to the 



* This research was supported in part by grants from the Office of Naval 

 Reseach and the American Cancer Society. 



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