Ketolysis

In addition to these interconversions, the metabolism of fat and the metabolism of carbohydrate are inseparably related. This fact is most clearly demonstrated by the appearance of such abnormal products of fat oxidation as the so-called ketone bodies in the blood and urine whenever the supply of carbohydrate is deficient or in cases where the organism is unable to metabolize this foodstuff. Whether ketonuria results because the metabolism of fat must occur concomitantly with that of D-glucose (ketolysis), or whether the presence of D-glucose prevents any fat breakdown because it is preferentially oxidized (antiketogenesis) is still a moot question. 

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. 

Another phenomenon which is difficult to interpret on the ketolysis basis is the finding that the rate of utilization of the ketones rises sharply with increased concentrations in the blood and tissues. The quantities oxidized under such circumstances apparently have no relationship to the carbohydrate utilized. In fact, they may practically exclude the oxidation of other metabolites since they have been reported to account for 90% of the total oxygen consumption at sufficiently high concentrations. However, such levels of ketones are never found normally and possibly a different relationship to carbohydrate occurs at physiological values. Likewise it is not clear whether a similar response would be expected if the natural isomer alone were administered. 

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. 

The reaction of D-glucose with ethyl acetoacetate was originally studied with a view to obtaining experimental information which would be useful in the interpretation of the biological phenomena of antiketogenesis. It is accepted that some kind of correlation exists between the metabolism of carbohydrates and that of /3-ketonie compounds, but views as to its nature differ. The supporters of the ketolysis theory1 contend that the oxi-... 

Diabetes - insulin dependent Methyl malonic, propionic or isovaleric acidaemias Pyruvate carboxylase and multiple carboxylase deficiency Gluconeogenesis enzyme deficiency glucose-6-phosphatase, fructose-1,6-diphosphatase or abnormality of glycogen synthesis (glycogen synthase) Ketolysis defects Succinyl coenzyme A 3-keto acid transferase ACAC coenzyme A thiolase... 

Saudubray JM, Specola N, Middleton B, Lombes A, Bonnefont JP, Jakobs C, Vassault A, Char-pentier C, Day R (1987) Hyperketotic states due to inherited defects of ketolysis. Enzyme 38 80-90... 

Ketals, of hexitols, IV, 223 Ketene, acetylation of starch with, I, 290 Keto acids, a- and 0-, specificity of carboxylase action on, V, 50 a-Keto acids, aromatic, V, 50 0-Keto acids, oxidation of, II, 148 a-Ketobutyric acid, V, 50 a-Ketocaproio acids, V, 50 Ketogenesis, in liver slices, II, 155 Ketolysis, II, 120, 146, 147, 158 in liver slices, II, 155 Ketolytic, II, 146... 

Other energy depletion disorders include disorders of fatty acid oxidation, ketone disorders (both synthesis and ketolysis), and disorders of glucose metabolism. These often present with a global neurologic phenotype resulting in altered mental status and/or seizures. Often these are in... 

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