Skip to main content
Log in

Transport of 3-hydroxybutyrate by cultured rat brain astrocytes

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

It is well established that 3-hydroxybutyrate can serve as an energy source for the brain. Since substrate utilization may be regulated in part by transport across the cellular membrane, we investigated the uptake of 3-hydroxybutyrate by primary cultures of rat brain astrocytes. Measurement of the net uptake indicated a saturable system and a Lineweaver-Burke type plot was consistent with a single carrier-mediated mechanism with a Km of 6.03 mM and a Vmax of 32.7 nmol/30 seconds/mg protein. The rate of uptake at pH 6.2 was more than ten times the rate at pH 8.2, with the rate at pH 7.4 being intermediate between these values, suggesting the possibility of cotransport with H+ or exchange with OH (antiport). Mersalyl had only a slight effect on the transport of 3-hydroxybutyrate, suggesting that sulfhydryl groups are not involved in the transport of this monocarboxylic acid. Phenylpyruvate and α-ketoisocaproate also attenuated the transport, but lactate had only a marginal effect. These results suggest that the utilization of 3-hydroxybutyrate as an energy source by astrocytes is regulated in part by carrier-mediated transport and that the uptake system is different from the lactate transport system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kraus, H., Schlenker, S., and Schwedesky, D. 1974. Developmental changes of cerebral ketone body utilization in human infants. Hoppe-Seyler's Z. Physiol. Chem. 355:164–170.

    Google Scholar 

  2. Persson, B., Settergsen, G., and Dahlquist, G. 1975. Cerebral arteriovenous difference of acetoacetate and 3-hydroxybutyrate. Acta Paediatr. Scand. 61:273–278.

    Google Scholar 

  3. Robinson, A. M. and Williamson, D. H. 1980. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol. Rev. 60:143–189.

    Google Scholar 

  4. Hawkins, R. A., Williamson, D. H. and Krebs, H. A. 1971. Ketone body utilization by adult and suckling rat brain in vivo. Biochem. J. 122:13–18.

    Google Scholar 

  5. Cremer, J. E. Nutrients for the brain. Problems in supply. 1982. Early Hum. Develop. 5:117–132.

    Google Scholar 

  6. Page, M. A., Krebs, H. A., and Williamson, D. H. 1971. Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats. Biochem. J. 121:49–53.

    Google Scholar 

  7. Middleton, B. 1973. The acetoacetyl CoA thiolases of rat brain and their relative activities during postnatal development. Biochem. J. 132:731–737.

    Google Scholar 

  8. Tildon, J. T., Cone, A. L., and Cornblath, M. 1971. Coenzyme A transferase activity in rat brain. Biochem. Biophys. Res. Commun. 148:382–390.

    Google Scholar 

  9. Roeder, L. M., Tildon, J. T., and Holman, D. C. 1984. Competition among oxidizable substrates in brains of young and adult rats: dissociated cells. Biochem. J. 219:131–135.

    Google Scholar 

  10. Roeder, L. M., Tildon, J. T., and Stevenson, Jr., J. H. 1984. Competition among oxidizable substrates in brains of young and adult rats: whole homogenates. Biochem. J. 219:125–130.

    Google Scholar 

  11. Daniel, P. M., Love, E. R., Moorhouse, S. R., and Pratt, O. E. 1977. The transport of ketone bodies into the brain of the rat (in vivo). J. Neurol. Sci. 34:1–13.

    Google Scholar 

  12. Gjedde, A., and Crone, C. 1975. Induction processes in blood brain transfer of ketone bodies during starvation. Am. J. Physiol. 229:1165–1169.

    Google Scholar 

  13. Pollay, M., and Steven, F. A. 1980. Starvation induced changes in transport of ketone bodies across the blood brain barrier. J. Neurosci. Res. 5:163–172.

    Google Scholar 

  14. Tildon, J. T., and Roeder, L. M. 1988. Transport of 3-hydroxy[3-14C]butyrate by dissociated cells from rat brain. Am. J. Physiol. 255 (Cell Physiol. 24) C133–139.

    Google Scholar 

  15. Shank, R. P., and Campbell, G. LeM. 1984. α-ketoglutarate and malate uptake and metabolism by synaptosomes: Further evidence for an astrocyte-to-neuron metabolic shuttle. J. Neurochem. 42: 1153–1161.

    Google Scholar 

  16. Shank, R. P., and Campbell, G. LeM. 1984. Amino acid uptake, content and metabolism by neuronal and glial enriched cellular fractions from mouse cerebellum. J. Neurosci. 4:58–69.

    Google Scholar 

  17. Yu, A. C., Hertz, E., Schousboe, A., and Hertz, L. 1984. Uptake and metabolism of malate in cultures of astrocytes and neurons. Trans. Am. Soc. Neurochem. 15:A216.

    Google Scholar 

  18. Auestad, N., Korsak, R. A., Marrow, J. W. and Edmond, J. 1991. Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J. Neurochem. 56:1376–1386.

    Google Scholar 

  19. Edmond, J., Robbins, R. A., Bergstron, J. D., Cole, R. A., and deVellis, J. 1987. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes and oligodendrocytes from developing brain in primary culture. J. Neurosci. Res. 18:551–561.

    Google Scholar 

  20. McKenna, M. C., Tildon, J. T., Couto, R., Stevenson, J. H., and Caprio, F. J. 1990. The metabolism of malate by cultured rat brain astrocytes. Neurochemical Research 15:1211–1220.

    Google Scholar 

  21. Tildon, J. T., McKenna, M. C., Stevenson, J. H., and Couto, R. 1993. Transport of L-lactate by cultured rat brain astrocytes. Neurochemical Research 18:177–184.

    Google Scholar 

  22. Roeder, L. M., Tildon, J. T., and Williams, I. B. 1985. Transport of 2-deoxy-D-glucose by dissociated brain cells. Brain Res. 345: 289–305.

    Google Scholar 

  23. Zielke, H. R., Tildon, J. T., Landry, M. E. and Max, S. R. 1990. Effect of 8-Bromo-cAMP and dexamethasone on glutamate metabolism in rat astrocytes. Neurochem. Res. 15:1115–1122.

    Google Scholar 

  24. Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., and Klenk, D. C. 1985. Measurement of protein using bicinchoninic acid. Anal. Biochem. 150:76–85.

    Google Scholar 

  25. Spencer, T. L., and Lehninger, A. L. 1976. L-lactate transport in Ehrlich ascites-tumor cells. Biochem. J. 154:405–414.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tildon, J.T., McKenna, M.C. & Stevenson, J.H. Transport of 3-hydroxybutyrate by cultured rat brain astrocytes. Neurochem Res 19, 1237–1242 (1994). https://doi.org/10.1007/BF01006812

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01006812

Key Words

Navigation