Enzymes 57 



trolled by the respiratory enzymes and may be listed as failure of 

 ATP synthesis, loss of coenzymes especially DPN and TPX, loss of 

 -SH groups and (for rat liver) loss of liver glycogen. There is in 

 addition disruption of water and electrolyte balance, and secondary 

 to failure of energy supply, failure of a wide range of complex 

 synthetic reactions. Other aspects of this matter are dealt with in the 

 chapter on Autolysis. 



SPECIFIC RESPIRATORY POISONS 



The behaviour of liver cells removed from the blood supply 

 has been used as an illustration of the vulnerability of the respira- 

 tory enzyme system to injury in the broadest sense of the term. 

 There are, however, many poisons and deficiency states known to 

 injure this system by causing a failure at one or more specific sites 

 in the complicated cycle of reactions. Some toxic compounds of this 

 nature associated with characteristic pathological lesions are dis- 

 cussed in the chapter on Toxic Agents. Others will be described 

 briefly here, (see also Hunter, 1955, and Brit. Med. Bull., 1954) . 



Cyanide 



The classical example is cyanide, which in small amounts leads 

 to rapid death. Cyanide acts by specific inhibition of the enzyme 

 cytochrome oxidase which is required for the transfer of electrons 

 from cytochrome to oxygen (Fig. 3) . The mode of action of cyanide 

 is to form a complex with the metal prosthetic group which is an 

 essential part of the cytochrome oxidase molecule. As a result, the 

 enzyme is inactivated and all oxidative reactions come to a stand- 

 still. 



2:4 dinitrophenol 



A similar example is provided by 2:4 dinitrophenol (DNP). 

 This substance prevents specifically the synthesis of ATP, while 

 allowing the associated oxidations to proceed (Fig. 6) . As a result, 

 the generated energy is dissipated as heat, and is no longer available 

 for the bodily reactions that require it. To compensate for this 

 failure there is a vain attempt to oxidise all available substrate and 



