GERARD: NERVE METABOLISM AND FUNCTION 577 



energy to do necessary work, such as to maintain polarization across 

 a leaky membrane, or it removes unwanted substances, or produces re- 

 (lui)'ed ones. Further, the change in concentration of a substance may 

 or may not be a needed step in the event of functioning, an indis- 

 pensable gear in the cell machine. 



In a particular case, it is often a teasing problem to determine just 

 what role a metabolic event plays in a tissue's function. The formation 

 of lactate in muscle contraction is a perfect illustration. When this 

 relation was first established, early this century, lactic acid was at once 

 assigned the key role of initiating shortening. It was an essential gear 

 and, perhaps by changing surface tension due to acidity, engaged the 

 shortening mechanism. Its removal or neutralization permitted re- 

 laxation. Later, attention to energy balance emphasized that glycolysis 

 could supply the energy required in anaerobic contraction and that this 

 reaction was largely rewound with oxidative metabolism in oxygen. 

 It was an easy assumption, then, even under aerobic conditions when 

 no lactate change was found, that there was a rapid formation and 

 destruction of this substance. Indeed, lactic acid was considered the 

 essential link between metabolism, of which it was a necessaiy inter- 

 mediate, and contraction, of which it was a necessary cause, and it 

 was supposedly involved in both energetics and mechanics. 



lodoacetic acid, alactic contractions, phosphocreatin and adenosine 

 triphosphate changes, and, finally, the use of lipid fuels (not to mention 

 myosin) , changed all that.*^ Muscle did not require lactic or any other 

 acid to shorten it ; lactate is not part of the machinery. The CrP and 

 ATP breakdown supplied the early energy needed for contraction, heat, 

 and work; lactate formation is not an immediate energy source. Mod- 

 erate exercise with good oxygenation involved no lactate change and 

 little carbohydrate loss; lactate is in no way necessary to contraction. 

 It is just one of the many initial or intermediate fuels available to the 

 engine under normal working conditions, and its accumulation anaero- 

 bically is, in a sense, a sign of failure to complete the initiated 

 oxidations. 



In a particular case, further, it is well to note that historical acci- 

 dents greatly influence the trend of our scientific thought and research. 

 Acetylcholine first came to attention as a pharmacologic agent; ATP, 

 as an intracellular substance involved in important metabolic sequences. 

 The great experimental sweeps were, accordingly, oriented differently 

 in the two cases. Yet ATP also has profound pharmacological ac- 

 tions,'- **• *• and ACh may well prove to be an important compon^ 

 cell metabolic systems in general. This point will require 

 later. 



