100 H. A. Krebs 



transport from different types of substrates to Og. It differs 

 in two respects from earlier schemes. One concerns the role 

 of vitamin K. Martins (1956) has provided evidence suggest- 

 ing that vitamin K is an essential link which might replace 

 flavoprotein in some cases. The other concerns the role of 

 flavoprotein in hydrogen transport from succinate. That 

 flavoprotein is required in this case has recently been estab- 

 lished by Green, Mii and Kohout (1955) and Kearney and 

 Singer (1955). 



The differences in the complexity of the various dehydro- 

 genase systems are reflected by differences in their behaviour 

 towards extraneous agents. It has long been known that the 

 oxidation of a-ketonic acids is sensitive to reagents, for 

 example, arsenite (Krebs, 1933), which do not affect other 

 dehydrogenases. Arsenite reacts with SH groups and the 

 specific action of arsenite on the oxidation of a-ketonic acids 

 can be understood on account of the special role played by 

 sulphydryl compounds in the dehydrogenation of a-ketonic 

 acids. 



The relative simplicity of the succinic dehydrogenase 

 system explains the fact that the oxidation of this substrate 

 is more stable towards environmental changes than that of 

 other substrates. Depriving the tissue of soluble cof actors by 

 washing of minced material with water, inactivates all major 

 dehydrogenase systems except succinic dehydrogenase. 



Examples of inhibitors of Class III acting at a branching 

 point of metabolism are agents inducing the formation of 

 ketone bodies in the liver. Among the pathways open to 

 acetyl coenzyme A in liver, there is the condensation with 

 oxaloacetate (i.e. entry into the tricarboxylic acid cycle) or 

 the condensation with another molecule of acetyl coenzyme 

 A [i.e. formation of acetoacetate ("ketogenesis")]. The 

 first requires oxaloacetate as a reactant, and much of the 

 evidence is in accordance with the view that the steady-state 

 level of oxaloacetate is a key factor in the control of keto- 

 genesis. 



Agents which reduce the supply of oxaloacetate in the 



