1. Iron spicules found in the brains of general paretic patients are formed from endogenous brain iron normally present in another form. This supports our earlier view that the µ value of 16,000 obtained in advanced paretics for alpha brain wave frequencies as a measure of cortical respiration comes about from the slowing of an iron catalyzed link in cortical respiration such as would result from the reduction of available cytochrome and its oxidase, thus making this step a chemical pacemaker.

2. To test the basic theory of chemical pacemakers, a study was made of the succinate-fumarate enzyme system containing succino-dehydrogenase and cytochrome-cytochrome oxidase acting sequentially.

3. The µ value for the unpoisoned system is 11,200 ± 200 calories.

4. According to theory, the addition of a critical amount of cyanide known to be a specific poison of the cytochrome-cytochrome oxidase system (and not of the dehydrogenase) should shift the µ cleanly to 16,000 calories, and it does.

5. According to theory, selenite, a specific poison for the dehydrogenase, should stop all respiration without shifting the µ. This also is found to be the case.

6. The theory also predicts that if the µ is shifted from 11,000 ± to 16,000 ± by cyanide, the subsequent addition of a critical amount of selenite should shift the µ back again to 11,000 ± calories, and this is found to occur.

7. It is concluded that approximately 11,000 calories is the energy of activation of the succino-dehydrogenase-catalyzed step and 16,000 calories is that for the cytochrome-cytochrome oxidase-catalyzed step. These two values are encountered more frequently than any others in physiological systems. It is to be recalled that a shift of µ for alpha brain wave frequencies from 11,000 to 16,000 calories occurs in the course of advancing syphilitic brain infection and is accompanied by a change in form of brain iron.

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