Rate-limiting Factors in Cell Respiration 3 



accelerated or slowed down rather than brought into play 

 anew. One of the main problems, therefore, in the analysis of 

 regulation is the identification of those component reactions 

 which are rate-limiting. 



The system on which I propose to illustrate some aspects of 

 the problem is a heart muscle homogenate. Muscle, striated 

 or cardiac, shows great variations in its rate of respiration 

 depending on the physiological state of the organ. It may 

 increase many times over when the muscle changes from rest 

 to activity. This is not a matter of hormonal action (although 

 hormones contribute to the control of the basal metabolic 

 rate). Variations in the rate of respiration are also encountered 

 in muscle suspensions incubated in vitro under different con- 

 ditions. For example, the rates of oxygen consumption vary 

 with the nature of the available substrate. This is illustrated 

 by Table I, which presents data on the oxygen consumption 



Table I 

 Oxygen used by 4 ml. sheep heart muscle homogenate 



CONTAINING 10 PER CENT TISSUE ; 20° ; 60 MIN. 



O2 used 

 Substrate added {\xmoles) 



none 17*0 



pyruvate 26 • 1 



succinate 32 • 6 



L-lactate 21-6 



citrate 20-8 



a-oxoglutarate 25*4 



fumarate 19 • 1 



acetate 21 ■ 1 



glycogen 15*4 



of a suspension of homogenized sheep heart in a saline medium 

 containing potassium chloride, magnesium chloride and 

 phosphate buffer. The tissue concentration was 10% (w/v). 

 Such a suspension absorbs oxygen very rapidly and in order 

 to eliminate diffusion as a limiting factor it is necessary to 

 work at 20°. Even at that temperature 4 ml. suspension may 

 use up to 20 \tX. O2 per min. There is no appreciable increase in 

 the rate of oxygen consumption when glucose or glycogen is 



