34 A SYMPOSIUM ON RESPIRATORY ENZYMES 



school, by Stare and Baumann, and, in connection with work on the 

 citric acid cycle, by Krebs and coworkers, and also by various other 

 workers. Krebs has also shown that at least the succinate-fumarate 

 mediation can occur in B. coli (Escherichia coli). If we assume that 

 the evidence for the Szent-Gyorgyi mechanism actually proves that 

 it does operate in pigeon breast muscle (see, however, addendum 

 below), the following questions arise: 



1. In what tissues may the mechanism he important? Tissues 

 other than pigeon muscle have not been studied exhaustively from 

 this point of view. One of the main tests for the system consists in 

 finding increased or better maintained respiration when small 

 amounts of fumarate or malate, which are interconvertible by tissue 

 fumarase, are added to the tissue brei. Our experience with this 

 test and that of other workers suggests that the system may be im- 

 portant for the respiration of liver, testis, and possibly kidney, but 

 is not very active in brain or skeletal muscle. However, individual 

 reactions of the system, namely, succinate oxidation and oxalacetate 

 reduction, occur rapidly in all these tissues, and Banga, Cori, and 

 coworkers have shown that the presence of fumarate is necessary 

 for the oxidation of pyruvate by kidney and brain dispersions. 

 Banga showed that it was not easy to remove all the four-carbon 

 acids from tissue. It is therefore possible that when added four- 

 carbon dicarboxylic acids have little effect on the respiration of 

 tissues, these substances may already be present in the tissues in 

 such amounts that their concentration is not a limiting factor of the 

 respiration rate. 



The volume of respiration passing through the system would be 

 limited by the activity of the relevant enzymes. Dr. Greig and I 

 found that there was sufficient cytochrome-cytochrome oxidase and 

 succinic dehydrogenase activity in many normal tissues to account 

 for all the respiration through succinate-fumarate, but the succinic 

 dehydrogenase activity was quite low in chick embryo, rat thymus, 

 spleen, pancreas, and some tumors. Breusch found that the rates of 

 oxalacetate reduction were high in muscle, liver, and kidney and 

 moderate in brain and pancreas, but negligible in spleen, lung, 

 placenta, peripheral nerves, and certain rat tumors; the rate in 

 embryo was found to be low by Blaszo. 



2. Does the four-carbon dicarboxylic acid system always operate 

 in the same waif? Szent-Gyorgyi himself pointed out that not all 

 substances should be expected to utilize the whole system. Lactate, 

 for instance, might be oxidized through fumarate-succinate but 



