KM) 



MARTIN G. LARRABEE AND PAUL HOROWICZ 



B 



0, POSSIBLY USEO 



FOR OXIDATION OF 



GLUCOSE 



FREQUENCY OF STIMULATION 



Fig. 9. Comparison of (A) the rate at which oxygen was consumed by rat ganglia 

 during supramaximal stimulation of the preganglionic nerve with (B), the rate at 

 which oxygen would be required to oxidize the glucose which was consumed but was 

 not converted to lactate. 



tween these two curves must represent oxidation of substrates other than 

 glucose — in other words endogenous substrates under the conditions of these 

 experiments. 



The conclusion of Holmes, Gerard and Solomon (1930) and of Mullins 

 (1953), that the substrate for activity metabolism is not glucose, is thus sup- 

 ported and extended to an example of nervous tissue in another species; more- 

 over, to a tissue which contains cell bodies and synapses as well as axons. In 

 contrast with the older work we now find that glucose utilization is accelerated 

 during activity. However, the final conclusion concerning the substrate for 

 activity is the same, since this does not appear to be glucose. We may also 

 recall recent evidence of Geiger, Magnes, and Dobkin (1954) that the extra 

 glucose consumed in perfused cat brain during convulsions is all converted to 

 lactate, just as in ganglia during activity. 



Other examples of parallel changes in glucose uptake and lactate output. Con- 

 version of the extra glucose consumed during activity, into lactate instead of 

 into oxidation products, could conceivably be due to a rate-limiting step, operat- 

 ing at a maximal rate even under normal resting conditions, somewhere be- 

 tween pyruvate and the Krebs cycle. In this connection it is relevant to men- 

 tion two other circumstances in which acceleration of glucose uptake was 

 accompanied by an equal acceleration of lactate production. 



One example was the spontaneous increase in rates during the course of an 

 experiment, mentioned earlier in this paper. Thus, in the average of a number 

 of experiments, glucose uptake increased about 30% in the first 5 hours after 

 excision, while lactate output nearly doubled. However, the difference between 

 the absolute rates, which represented the amount of glucose available for oxi- 

 dation, showed no significant alteration. 



The other circumstance in which acceleration of glucose uptake was matched 



