Abstract
Extract: Studies of substrate oxidation by cultured skin fibroblasts from an infant (CC) with severe recurrent episodes of ketoacidosis showed normal rates of oxidation of pro-pionate (CC 55. ± 8 versus control 65 ± 13 μμmoles/mg protein/hr), and succinate (73. ± 16 versus 45 ± 8 μμmoles/mg protein/hr).
In contrast, both oxidation and uptake of glucose by these cells were decreased in comparison with controls. Essentially neither glucose-6-14C nor glycerol-U-14C was converted to 14CO2 by fibroblasts of the patient, and glucose-1-14C was oxidized at 45–65% of control rates. In the absence of glucose, oxidation of pyruvate-2-14C did not differ from that of normal controls (710 versus 940 μμmoles/mg protein/hr). In the presence of 2.5 mM glucose, however, fibroblasts of the patient did not show the expected decrease in pyruvate-2-14C oxidation whereas control cells showed a fourfold decrease. Studies of glucose uptake demonstrated that with glucose as the only substrate extended incubation periods of 12–18 hr were necessary before the cells of the patient began to utilize measurable quantities of glucose.
The results of the metabolic studies in skin fibroblasts, when viewed in conjunction with the clinical manifestations and laboratory studies, have excluded the known causes of infantile ketoacidosis. The data reported indicate a correlation of this form of ketoacidosis with a block in the terminal pathway of glycolysis.
Speculation: A defect in glycolysis may produce intracellular hypoglycemia resulting in the activation of unknown mechanisms in peripheral tissue that initiate lipolysis and ketosis. It could also be that a yet undefined block in ketoacid metabolism might result in the observed irregular glucose oxidation. The basic abnormality may be a result of an in-balance in redox cofactors, an absence of a critical intermediate, or a reduction of an end product. These possibilities are currently being investigated.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tildon, J., Leffler, A., Cornblath, M. et al. Abnormal Glucose Metabolism in Skin Fibroblasts Cultured from a Patient with a New Syndrome of Ketoacidemia. Pediatr Res 5, 518–522 (1971). https://doi.org/10.1203/00006450-197110000-00004
Issue date:
DOI: https://doi.org/10.1203/00006450-197110000-00004
