RESPIRATION 683 



isolated enzyme systems. This might be due to the fact that respiration is 

 the sum of a variety of reactions utilizing oxygen, the sensitivities to the 

 arsenicals varying widely, but if this is so it indicates that inhibition of 

 the keto acid oxidations is by no means the sole cause of the depression of 

 respiration. It may also be noted in the curves in Fig. 6-4 that they tend 

 to level off at inhibitions significantly lower than 100%, and this is well seen 

 in several examples in Table 6-7, where progressive rise of the arsenical 

 concentration above a certain level produces no further inhibition (e. g., 

 Nocardia, Allomyces, yeast, corn root tips. Trichomonas, frog nerve, and 

 guinea pig brain). In addition, one finds several instances in which high 

 concentrations inhibit poorly (e. g., Thiohacillus, the mycobacteria, Peni- 

 cillinm, and carrot). Indeed, it is uncommon to find complete respiratory 

 inhibition by an arsenical. It is, therefore, of some interest to inquire as 

 to the nature of the arsenical-resistant respiration. (1) In some instances 

 impermeability of the cell for the arsenical may account for a weak effect 

 on respiration, but this will hardly explain the levelling off of the concen- 

 tration-inhibition curves, nor does it seem to apply to the results with 

 arsenite (although see page 698). (2) The oxidation of arsenite by enzymes 

 might contribute occasionally but can scarcely be a major factor. (3) The 

 keto acid oxidases of certain microorganisms are rather insensitive to the 

 arsenicals, but again this would apply only rarely. (4) The respiration is 

 partly attributable to oxidations not involving the cycle or keto acid oxida- 

 tion in most cells. Such oxidations include those of fatty acids, amino acids, 

 glucose, and glucose-6-P, these systems often being quite resistant to the 

 arsenicals. (5) Pathways normally not significantly contributory may be 

 utilized in the presence of arsenicals, particularly in microorganisms ca- 

 pable of metabolizing pyruvate in different ways. However, these are all 

 speculations and we do not know in any case what the nature of the resistant 

 respiration is. Generally the respiration in the presence of glucose is more 

 sensitive than the endogenous respiration, but the difference is seldom 

 marked and occasionally the opposite effect is observed; this might depend 

 on whether glucose or its phosphorylated products can be directly oxidized. 

 The concentration-inhibition curves often exhibit a range in which 

 respiratory stimulation occurs, and probably many more instances of this 

 would be known if lower concentrations of the arsenicals had been used. 

 This is characteristic of most SH reagents but the mechanism is unknown 

 (see page 11-879 where this problem is discussed in relation to the mercurials). 

 A more unique respiratory response was noted by Graham (1946) in insect 

 larvae, the inhibition disappearing as the arsenite concentration is raised. 

 The results of Schmitt et al. (1934) on nerve may indicate a similar phe- 

 nomenon but since the experiments were done at varying temperatures 

 one cannot be certain. This possibly represents an injury response, arsenical- 

 resistant oxidative processes being initiated, and since it was noted with 

 other inhibitors is not a characteristic of the arsenicals. 



