Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1973 Jan;70(1):210–214. doi: 10.1073/pnas.70.1.210

An Alteration in Glucose Metabolism Associated with a Defect in Ketone Body Metabolism

J Tyson Tildon 1,2
PMCID: PMC433217  PMID: 4509653

Abstract

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 [6-14C]glucose to 14CO2 by these cells was also significantly diminished (12 against 350 pmol/mg per hr), but [2-14C]pyruvate and [1,4-14C]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, [6-14C]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.

Keywords: skin fibroblasts, coenzyme A, transferase, pyruvate, Embden-Myerhof pathway

Full text

PDF
210

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CRISTOFALO V. J., KRITCHEVSKY D. GROWTH AND GLYCOLYSIS IN THE HUMAN DIPLOID CELL STRAIN WI-38. Proc Soc Exp Biol Med. 1965 Apr;118:1109–1113. doi: 10.3181/00379727-118-30057. [DOI] [PubMed] [Google Scholar]
  2. Condon M. A., Oski F. A., DiMauro S., Mellman W. J. Glycolytic difference between foetal and non-foetal human fibroblast lines. Nat New Biol. 1971 Feb 17;229(7):214–215. doi: 10.1038/newbio229214a0. [DOI] [PubMed] [Google Scholar]
  3. Cornblath M., Gingell R. L., Fleming G. A., Tildon J. T., Leffler A. T., Wapnir R. A. A new syndrome of ketoacidosis in infancy. J Pediatr. 1971 Sep;79(3):413–418. doi: 10.1016/s0022-3476(71)80149-x. [DOI] [PubMed] [Google Scholar]
  4. Cristofalo V. J., Kritchevsky D. Respiration and glycolysis in the human diploid cell strain WI-38. J Cell Physiol. 1966 Feb;67(1):125–132. doi: 10.1002/jcp.1040670114. [DOI] [PubMed] [Google Scholar]
  5. EAGLE H., OYAMA V. I., LEVY M., HORTON C. L., FLEISCHMAN R. The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J Biol Chem. 1956 Feb;218(2):607–616. [PubMed] [Google Scholar]
  6. FRIEDLAND I. M., DIETRICH L. S. A rapid enzymic determination of L-lactic acid. Anal Biochem. 1961 Aug;2:390–392. doi: 10.1016/0003-2697(61)90014-8. [DOI] [PubMed] [Google Scholar]
  7. Griffiths J. B. The quantitative utilization of amino acids and glucose and contact inhibition of growth in cultures of the human diploid cell, WI-38. J Cell Sci. 1970 May;6(3):739–749. doi: 10.1242/jcs.6.3.739. [DOI] [PubMed] [Google Scholar]
  8. Hsia Y. E., Scully K. J., Rosenberg L. E. Inherited propionyl-Coa carboxylase deficiency in "ketotic hyperglycinemia". J Clin Invest. 1971 Jan;50(1):127–130. doi: 10.1172/JCI106466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kruse P. F., Jr, Miedema E. Glucose uptake related to proliferation of animal cells in vitro. Proc Soc Exp Biol Med. 1965 Aug-Sep;119(4):1110–1112. doi: 10.3181/00379727-119-30389. [DOI] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Lowry O. H., Carter J., Ward J. B., Glaser L. The effect of carbon and nitrogen sources on the level of metabolic intermediates in Escherichia coli. J Biol Chem. 1971 Nov;246(21):6511–6521. [PubMed] [Google Scholar]
  12. MARKS V. An improved glucose-oxidase method for determining blood, C.S.F. and urine glucose levels. Clin Chim Acta. 1959 May;4(3):395–400. doi: 10.1016/0009-8981(59)90110-x. [DOI] [PubMed] [Google Scholar]
  13. Morrow G., 3rd, Mellman W. J., Barness L. A., Dimitrov N. V. Propionate metabolism in cells cultured from a patient with methylmalonic acidemia. Pediatr Res. 1969 May;3(3):217–219. doi: 10.1203/00006450-196905000-00005. [DOI] [PubMed] [Google Scholar]
  14. Moulder J. W. Glucose Metabolism of L Cells Before and After Infection with Chlamydia psittaci. J Bacteriol. 1970 Dec;104(3):1189–1196. doi: 10.1128/jb.104.3.1189-1196.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Okada S., O'Brien J. S. Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component. Science. 1969 Aug 15;165(3894):698–700. doi: 10.1126/science.165.3894.698. [DOI] [PubMed] [Google Scholar]
  16. Tildon J. T., Cornblath M. Succinyl-CoA: 3-ketoacid CoA-transferase deficiency. A cause for ketoacidosis in infancy. J Clin Invest. 1972 Mar;51(3):493–498. doi: 10.1172/JCI106837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Warshaw J. B., Rosenthal M. D. Changes in glucose oxidation during growth of embryonic heart cells in culture. J Cell Biol. 1972 Feb;52(2):283–291. doi: 10.1083/jcb.52.2.283. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES