An alteration in glucose metabolism associated with a defect in ketone body metabolism.

Skin fibroblasts (CC-69) cultured from a patient with a unique syndrome of ketoacidosis associated with coenzyme A transferase (EC 2.8.3.5) deficiency showed an altered pattern of carbohydrate metabolism. These cells used glucose at a rate significantly less than controls (125 against 680 nmol/mg per hr). The oxidation of [6-(14)C]glucose to (14)CO(2) by these cells was also significantly diminished (12 against 350 pmol/mg per hr), but [2-(14)C]pyruvate and [1,4-(14)C]succinate oxidation by these cells did not differ from that by control cells. Measurements of glycolytic intermediates showed a reduction of several intermediates in the CC-69 cells that confirmed an inhibition of glycolysis between fructose-1,6-bisphosphate and pyruvate. The apparent inhibition in these cells could be reversed by an extended incubation of the cells in a buffered glucose solution. After 18 hr of incubation in 2.5 mM glucose, glucose uptake by the CC-69 cells increased 20-fold to 2560 nmol/mg per hr, whereas the rate for control cells remained constant at 640 +/- 90. Concomitant with this increase, [6-(14)C]glucose oxidation rose from 8 to 2261 pmol/mg per hr while controls remained constant at 428 +/- 175. This change was not due to new enzyme formation because incubation with puromycin had no effect on the increased use of glucose. Mixing experiments demonstrated no transfer of a permeable inhibitor or activating substances. In view of the deficiency of coenzyme A transferase in these cells, the data suggest an indirect regulatory role for this enzyme in peripheral tissue glycolysis.