Ketolysis Theory

As a result of the more recent work, it is apparent that the ketolysis theory as originally suggested by Shaffer should be somewhat modified. Observations such as those on the effect of concentration on the extent of oxidation of the ketones are difficult to explain on the basis of the original theory. 

The most serious objection to the ketolysis theory has been the report that D-glucose is without effect on the rate of disappearance of ketones in the animal body. This has, however, been denied by one group of investigators and it is possible that the divergent results might be ascribed to the use of the natural levorotatory isomer of /3-hydroxy-butyrate rather than the racemic salt employed by others. 

It would seem that normally the oxidation of ketone bodies would proceed largely to completion in the liver by the ketolytic mechanism. Whenever the supply of carbohydrates here is sufficiently reduced, appreciable amounts of ketones then escape oxidation and pass into the blood. When the concentration of ketones becomes sufficiently elevated, a ketonuria occurs and also some ketones will be utilized by the tissues. Such a theory would largely limit the ketolysis mechanism to the liver. It would explain the specificity of the sugars in preventing ketonuria and the discrepancy between the amount of D-glucose required to prevent ketosis and the caloric value of the fat spared. It is further supported by the demonstration that the liver is capable of exhibiting ketolysis. 

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