Extraneous Agents and Cell Metabolism 97 



mechanism controlling the branching points of metabolism and 

 can therefore divert metabolism from one pathway to another. 



Inhibitors belonging to Class I are hydrocyanic acid, azide, 

 carbon monoxide or sulphide which stop the electron transport 

 from iron porphyrin to molecular Og. Another example is 

 antimycin A which combines with an unidentified component 

 of the transport chain between dehydrogenase and cytochrome 

 c and therefore inhibits the oxidation of the substrate by 

 molecular oxygen whilst not preventing ferricyanide from 

 acting as an electron acceptor (Potter and Reif, 1952; Copen- 

 haver and Lardy, 1952). 



Inhibitors of Class II interfere at the dehydrogenase level. 

 If the inhibitor is specific for one dehydrogenase, or one type 

 of dehydrogenase, it does not necessarily alter the overall rate 

 of oxidation because other substrates can take the place of 

 that which is prevented from reacting. Thus, cells exposed 

 to malonate which can no longer oxidize succinate at the 

 usual rate may still consume oxygen at the normal rate, if 

 another substrate, such as fumarate, is available. 



The initial step of substrate degradation can be brought 

 about by several different types of reaction. In most cases 

 this is a more or less direct transfer to pyridine nucleotide 

 according to the general formula : 



dehydrogenase .,. , i .. . , 

 (1) substrate + DPN > oxidized substrate + 



DPNH2 



The a-ketonic acids require a more complex mechanism 

 which involves at least six additional cofactors : coenzyme A, 

 a-lipoic acid, cocarboxylase, ADP, GDP and inorganic phos- 

 phate. In the case of a-ketoglutarate the following reaction 

 mechanism has been formulated (Gunsalus, 1954). The initial 

 step is taken to be a reaction between a-ketoglutarate and 

 thiamine pyrophosphate (TPP) in which a succinic semialde- 

 hyde-TPP-complex is formed and COg liberated: 



R . CO . COOH + TPP -> [R . COH . TPP] -f CO^ 

 (R =C00H.(CH2),) 



RAD. 



