PHYSICOCHEMICAL FACTORS— BROWN 3 



reason to consider the luminescence reaction as the prototype of many groups of 

 intracellular processes, particularly in relation to temperature and chemical agents. 

 The temperature relations of the luminescence reaction arc typical of numerous 

 biological processes. W'itli increasing temperature, the rate of the reaction increases 

 in accordance with the .\rrhenius equation, reaches a maximum, and then decreases 

 (Brown, Johnson, Marsland, 1942). At low temi)eratures, the rate is determined by 

 the luminescence reaction with U. 16,000, while at high temperatures the rapid de- 

 crease in rate is controlled l)y the reversible thermal denaturation (RTD) of the 

 enzymatic proteins. The rate at intermediate temperatures then depends on the inter- 

 play between these opposing reactions. Concerning the RTD, a sufficient body of 

 evidence has accumulated to consider that it depends on a reconfiguration of the 

 protein enzymes, this being attended by a large increase in volume ( A\' 80-100 cc.) 

 and a heat equilibrium (H 50,000-80,000 cal.). 



The recognition that this typical temperature relation involves at least two quite 

 distinct reactions has opened the way to an understanding of the action of various 

 agents on cellular processes and enzymatic reactions in vitro. As a result of a most 

 extensive study of the action of inhibitors, F. H. Johnson and co-workers concluded 

 that in the simplest cases these agents fall into two classes, designated as Type I 

 and Type II. Among the Type I compounds are agents such as sulphanilamide and 

 certain anticholinesterases. These, it seems, combine with the prosthetic group of 

 the enzymes and, since the degree of association is temperature-dependent, they 

 become more effective at lower temperatures. In view of their mode of action, the 

 Type I compounds tend to compete with the substrate and are thus influenced by 

 variations in the effective substrate concentration. 



The Type II compounds, which include a large number of narcotics, encourage 

 the RTD and are thus greatly potentiated by a rise in temperature. Certain agents, 

 such as quinine, exhibit both Type I and Type II effects, indicating in all probability 

 that they are acting at more than one locus. The effectiveness of such agents is at 

 a minimum at intermediate temperatures but increases when the temperature is 

 raised or lowered. 



During recent years, the conclusions drawn from studies on bacterial luminescence 

 have been found to be applicable to many phenomena, such as growth, disinfection, 

 cardiac rhythmicity, contraction, cell division, and amoeboid motion. It seems cer- 

 tain that knowledge brought to light in this long series of studies may have an im- 

 portant bearing on the role of chemical agents in induced hypothermia. To allay any 

 doubts, the results of Overton on the anesthetization of tadpoles by ethyl alcohol 

 may be mentioned.' Here tadpoles, anesthetized at 20° C, tend to revive on being 

 cooled. Since this is the typical action of a Type II compound, Johnson and Flagler 

 (1951) argued that compression by reducing the volume of the protein enzymes 

 should revive the animals and proceeded to perform experiments to test the matter. 

 The results were as expected : on compression, anesthetized salamander larvae 

 resumed swimming, and on subsequent decompression they became inactive. 



The results of this simple but critical experiment give clear evidence that reac- 

 tions, similar to the luminescence reaction in their basic physicochemical relations, 

 are involved in the responses of a vertebrate to temperature and anesthetics. 



Another sort of reaction, differing from the luminescence type only in that the 



