Effect of succinate, fumarate, and oxalacetate on ketone body production by liver slices from non-diabetic and diabetic rats.

The metabolism of fatty acids involves the production of acetyl coenzyme A and its condensation with oxalacetate for complete oxidation in the citric acid cycle. The availability of oxalacetate can determine the extent of metabolism via the Krebs cycle (1). In the presence of a low level of oxalacetate in the liver, fatty acid metabolism should produce an excess of ketone bodies. Previously (2) we have demonstrated that the administration of various precursors of oxalacetic acid (succinic acid, malic acid, a-ketoglutaric acid, etc.) and oxalacetic acid itself decreases total urinary ketone body excretion in non-diabetic rats made ketotic by the administration of butyric acid. We have also shown (3) that the administration of succinic and malic acids in doses sufficient to produce increased glucosuria has no effect on the ketonuria of alloxan-diabetic rats fed Wesson oil. Furthermore, the administration of small amounts of insulin plus succinic or malic acid to our insulin-deficient preparation caused a larger decrease in ketonuria than when insulin alone was given. In the present investigation we have compared the effects of oxalacetic acid precursors such as fumarate on the production of ketone bodies by liver slices from normal and diabetic rats. Changes in oxygen consumption and in glucose production were also measured.