Abstract
In an infant with a unique form of persistent ketonemia and severe intermittent keto-acidosis, studies of post mortem brain, muscle and kidney tissue demonstrated the absence of CoA transferase, a critical enzyme in ketone metabolism. Other enzymes of glucose and ketone metabolism were present in both post mortem tissues and skin fibroblasts from this patient. The tissue culture fibroblasts in addition to having no CoA transferase activity, demonstrated an altered carbohydrate metabolism compared to that of normal cells. When initially harvested, these cells utilized glucose at a rate significantly less than that of controls (125 vs 680 mμM/mg/hr). However, after incubation of 2.5 mM glucose for 18 hours, glucose uptake by patient's cell increased 20 fold (2560 mμM/mg/hr) whereas, that by control cells remained constant (680 ± 90). Concomitant with this increase, glucose-6-14C oxidation to 14CO2 in patient's fibroblasts rose from 8 to 2261 μμM/mg/hr, while that in control cells remained constant (485 ± 175). This increase in glucose utilization was not due to new enzyme formation since incubation with puromycin had no effect. Mixing experiments demonstrated no transfer of permeable inhibitors or activating substances. These data indicate that the absence of CoA transferase was the probable cause of the keto-acidosis in this infant and of the abnormal glucose metabolism in the fibroblasts suggesting a regulatory role for this enzyme in peripheral tissue glycolysis.
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Tildon, J., Cornblath, M. Succinyl-CoA: 3-Ketoacid-CoA transferase (CoA transferase) deficiency, a new cause of keto-acidosis in infancy. Pediatr Res 5, 394 (1971). https://doi.org/10.1203/00006450-197108000-00095
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DOI: https://doi.org/10.1203/00006450-197108000-00095