174 III. OXIDATION AND METABOLISM 



shown to decrease spontaneous ketogenesis in liver sliees.^^^ Rat liver 

 and kidney, and most mammalian livers, were shown to possess a dehydro- 

 genase which catalyzes a reversible oxidation of sorbitol to D-fructose, and 

 of L-iditol to L-sorbose; coenzyme I is required for its activity.^^^ When 

 sorbitol is oxidized by liver slices, glucose is the main product. However, 

 Blakley^^^ later demonstrated that sorbitol is unable to alter the spontane- 

 ous ketonuria in liver homogenates. It was also found that the oxidation 

 of octanoate with acetoacetate formation in washed mitochondria suspen- 

 sions is unaffected by the simultaneous dehydrogenation of sorbitol. 

 Thus, under conditions in which a competition might exist for coenzyme 

 I or ATP, sorbitol dehydrogenation was without effect on fatty acid 

 oxidation. 



Thus, it is evident that glucose, other related sugars, glucose intermediates 

 (including some amino acids), and also the hexitols, are invariably able to 

 reduce ketonuria. The ability to reduce exogenous ketonuria is believed 

 to be a property inherent in glucose-forming compounds. 



d'. The Negative Effect of Non-Glucose Precursors on Ketonuria: 

 In contradistinction to the consistent ketolytic effect observed in the 

 case of all the glucose-forming intermediates discussed above, there is no 

 instance in which a ketolysis can be demonstrated with non-glycogenic 

 compounds. Thus, Shapiro^^" reported that DL-lactic acid, acetalde- 

 hyde, ethylene glycol, and ethyl alcohol had no effect on ketonuria; further- 

 more, these substances were not effective as sources of sugar, as judged by 

 liver glycogen studies. Similarly leucine, ^"^ and cystine^®^ are neither 

 glycogenic nor ketolytic. 



Shapiro'^'"' noted that, in a certain proportion of tests with ethyl alcohol 

 and ethylene glycol, a reduction in ketonuria obtained. However, this 

 effect was found only in cases in which a concomitant increase in protein 

 metabolism occurred. In no single instance was a reduction of the keto- 

 nuria observed when a simultaneous rise in protein metabolism was not 

 present. 



The negative ketolytic effect of cystine calls for comment. Dakin^^^ 

 obtained "extra sugar" when cysteine was fed as the sodium salt to phlo- 

 rhizinized dogs. One might naturally expect that cystine would respond 

 in a manner similar to that of cysteine. However, Butts et al.^^^ were 

 unable to demonstrate any deposition of liver glycogen, or a lowering in 

 the level of experimental ketonuria, after the administration of L-cystine 

 to rats in the form of a suspension. It was shown on the basis of the 



"1 R. L. Blaklev, Biochem. J., 49, 257-271 (1951). 

 "2 R. L. Blakley, Biochem. J., 52, 269-279 (1952). 



